Lisia Barros Ferreira, Keryn A Williams, Giles Best, Cameron D Haydinger, Justine R Smith
Characterised by intraocular inflammation, non-infectious uveitis includes a large group of autoimmune and autoinflammatory diseases that either involve the eye alone or have both ocular and systemic manifestations. When non-infectious uveitis involves the posterior segment of the eye, specifically the retina, there is substantial risk of vision loss, often linked to breakdown of the inner blood-retinal barrier. This barrier is formed by non-fenestrated retinal vascular endothelial cells, reinforced by supporting cells that include pericytes, Müller cells and astrocytes. Across the published literature, a group of inflammatory cytokines stand out as prominent mediators of intraocular inflammation, with effects on the retinal endothelium that may contribute to breakdown of the inner blood-retinal barrier, namely tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, IL-17 and chemokine C-C motif ligand (CCL)2. This article reviews the function of each cytokine and discusses the evidence for their involvement in retinal endothelial barrier dysfunction in non-infectious uveitis, including basic laboratory investigations, studies of ocular fluids collected from patients with non-infectious uveitis, and results of clinical treatment trials. The review also outlines gaps in knowledge in this area. Understanding the disease processes at a molecular level can suggest treatment alternatives that are directed against appropriate biological targets to protect the posterior segment of eye and preserve vision in non-infectious uveitis.
{"title":"Inflammatory cytokines as mediators of retinal endothelial barrier dysfunction in non-infectious uveitis","authors":"Lisia Barros Ferreira, Keryn A Williams, Giles Best, Cameron D Haydinger, Justine R Smith","doi":"10.1002/cti2.1479","DOIUrl":"https://doi.org/10.1002/cti2.1479","url":null,"abstract":"<p>Characterised by intraocular inflammation, non-infectious uveitis includes a large group of autoimmune and autoinflammatory diseases that either involve the eye alone or have both ocular and systemic manifestations. When non-infectious uveitis involves the posterior segment of the eye, specifically the retina, there is substantial risk of vision loss, often linked to breakdown of the inner blood-retinal barrier. This barrier is formed by non-fenestrated retinal vascular endothelial cells, reinforced by supporting cells that include pericytes, Müller cells and astrocytes. Across the published literature, a group of inflammatory cytokines stand out as prominent mediators of intraocular inflammation, with effects on the retinal endothelium that may contribute to breakdown of the inner blood-retinal barrier, namely tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, IL-17 and chemokine C-C motif ligand (CCL)2. This article reviews the function of each cytokine and discusses the evidence for their involvement in retinal endothelial barrier dysfunction in non-infectious uveitis, including basic laboratory investigations, studies of ocular fluids collected from patients with non-infectious uveitis, and results of clinical treatment trials. The review also outlines gaps in knowledge in this area. Understanding the disease processes at a molecular level can suggest treatment alternatives that are directed against appropriate biological targets to protect the posterior segment of eye and preserve vision in non-infectious uveitis.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 12","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1479","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138571055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katharina Robichon, Rabia Bibi, Mackenzie Kiernan, Lisa Denny, Thomas E Prisinzano, Bronwyn M Kivell, Anne Camille La Flamme
Objectives
Multiple sclerosis (MS) is a neurodegenerative disease characterised by inflammation and damage to myelin sheaths. While all current disease-modifying treatments (DMTs) are very effective at reducing relapses, they do not slow the progression of the disease, and there is little evidence that these treatments are able to repair or remyelinate damaged axons. Recent evidence suggests that activating kappa opioid receptors (KORs) has a beneficial effect on the progression of MS, and this study investigates the effects of KOR agonists treatment in combination with two current DMTs.
Methods
Using the well-established murine model for immune-driven demyelination of MS, experimental autoimmune encephalomyelitis, the effect of KOR agonists in combination with DMTs fingolimod or dimethyl fumarate on disease progression, immune cell infiltration and activation as well as myelination were analysed.
Results
Fingolimod in combination with the KOR agonist, nalfurafine, significantly increased each individual beneficial effect as measured by increased recovery of mice and reduced relapses. These beneficial effects correlated with a reduction in immune cell infiltration into the CNS as well as peripheral immune cell alterations including a reduction in autoreactive CD4+ T-cell cytokine production as well as increased myelination in the spinal cords of co-treated animals. In contrast, while the use of dimethyl fumarate in combination with nalfurafine did not adversely affect the benefits of nalfurafine, the combination did not significantly enhance those benefits.
Conclusion
This study indicates that KOR agonists can be used in combination with fingolimod and dimethyl fumarate with the nalfurafine–fingolimod combination providing enhanced benefits.
目标 多发性硬化症（MS）是一种以炎症和髓鞘损伤为特征的神经退行性疾病。虽然目前所有的改变病情疗法（DMTs）都能有效减少复发，但它们并不能延缓疾病的进展，而且几乎没有证据表明这些疗法能够修复或再髓鞘化受损的轴突。最近的证据表明，激活卡巴阿片受体（KORs）对多发性硬化症的进展有好处，本研究调查了KOR激动剂与目前两种DMTs联合治疗的效果。 方法 使用免疫驱动的多发性硬化脱髓鞘的成熟小鼠模型--实验性自身免疫性脑脊髓炎，分析 KOR 激动剂与 DMTs 芬戈莫德或富马酸二甲酯联用对疾病进展、免疫细胞浸润和活化以及髓鞘化的影响。 结果 芬戈莫德与 KOR 激动剂纳呋拉芬联用，能显著提高每种单药的疗效，具体表现为小鼠恢复能力增强，复发次数减少。这些有益效果与中枢神经系统免疫细胞浸润的减少以及外周免疫细胞的改变有关，包括自反应性 CD4+ T 细胞细胞因子产生的减少以及联合治疗动物脊髓髓鞘化的增加。相比之下，虽然富马酸二甲酯与纳呋拉芬联合使用不会对纳呋拉芬的疗效产生不利影响，但联合使用也不会显著增强这些疗效。 结论 本研究表明，KOR 激动剂可与芬戈莫德和富马酸二甲酯联用，纳呋拉芬-芬戈莫德联用可提高疗效。
{"title":"Enhanced and complementary benefits of a nalfurafine and fingolimod combination to treat immune-driven demyelination","authors":"Katharina Robichon, Rabia Bibi, Mackenzie Kiernan, Lisa Denny, Thomas E Prisinzano, Bronwyn M Kivell, Anne Camille La Flamme","doi":"10.1002/cti2.1480","DOIUrl":"https://doi.org/10.1002/cti2.1480","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Multiple sclerosis (MS) is a neurodegenerative disease characterised by inflammation and damage to myelin sheaths. While all current disease-modifying treatments (DMTs) are very effective at reducing relapses, they do not slow the progression of the disease, and there is little evidence that these treatments are able to repair or remyelinate damaged axons. Recent evidence suggests that activating kappa opioid receptors (KORs) has a beneficial effect on the progression of MS, and this study investigates the effects of KOR agonists treatment in combination with two current DMTs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the well-established murine model for immune-driven demyelination of MS, experimental autoimmune encephalomyelitis, the effect of KOR agonists in combination with DMTs fingolimod or dimethyl fumarate on disease progression, immune cell infiltration and activation as well as myelination were analysed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fingolimod in combination with the KOR agonist, nalfurafine, significantly increased each individual beneficial effect as measured by increased recovery of mice and reduced relapses. These beneficial effects correlated with a reduction in immune cell infiltration into the CNS as well as peripheral immune cell alterations including a reduction in autoreactive CD4<sup>+</sup> T-cell cytokine production as well as increased myelination in the spinal cords of co-treated animals. In contrast, while the use of dimethyl fumarate in combination with nalfurafine did not adversely affect the benefits of nalfurafine, the combination did not significantly enhance those benefits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study indicates that KOR agonists can be used in combination with fingolimod and dimethyl fumarate with the nalfurafine–fingolimod combination providing enhanced benefits.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 12","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1480","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138571043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marcus ZW Tong, Julian DJ Sng, Meagan Carney, Lucy Cooper, Samuel Brown, Katie E Lineburg, Keng Yih Chew, Neve Collins, Kirsten Ignacio, Megan Airey, Lucy Burr, Briony A Joyce, Dhilshan Jayasinghe, Christopher LD McMillan, David A Muller, Anurag Adhikari, Linda A Gallo, Emily S Dorey, Helen L Barrett, Stephanie Gras, Corey Smith, Kim Good-Jacobson, Kirsty R Short
Objective
Class III obesity (body mass index [BMI] ≥ 40 kg m−2) significantly impairs the immune response to SARS-CoV-2 vaccination. However, the effect of an elevated BMI (≥ 25 kg m−2) on humoral immunity to SARS-CoV-2 infection and COVID-19 vaccination remains unclear.
Methods
We collected blood samples from people who recovered from SARS-CoV-2 infection approximately 3 and 13 months of post-infection (noting that these individuals were not exposed to SARS-CoV-2 or vaccinated in the interim). We also collected blood samples from people approximately 5 months of post-second dose COVID-19 vaccination (the majority of whom did not have a prior SARS-CoV-2 infection). We measured their humoral responses to SARS-CoV-2, grouping individuals based on a BMI greater or less than 25 kg m−2.
Results
Here, we show that an increased BMI (≥ 25 kg m−2), when accounting for age and sex differences, is associated with reduced antibody responses after SARS-CoV-2 infection. At 3 months of post-infection, an elevated BMI was associated with reduced antibody titres. At 13 months of post-infection, an elevated BMI was associated with reduced antibody avidity and a reduced percentage of spike-positive B cells. In contrast, no significant association was noted between a BMI ≥ 25 kg m−2 and humoral immunity to SARS-CoV-2 at 5 months of post-secondary vaccination.
Conclusions
Taken together, these data showed that elevated BMI is associated with an impaired humoral immune response to SARS-CoV-2 infection. The impairment of infection-induced immunity in individuals with a BMI ≥ 25 kg m−2 suggests an added impetus for vaccination rather than relying on infection-induced immunity.
III类肥胖(体重指数[BMI]≥40 kg m−2)显著损害对SARS-CoV-2疫苗接种的免疫应答。然而，BMI升高(≥25 kg m−2)对SARS-CoV-2感染的体液免疫和COVID-19疫苗接种的影响尚不清楚。方法我们采集了感染后约3个月和13个月从SARS-CoV-2感染中恢复的人的血液样本(注意这些人在此期间没有暴露于SARS-CoV-2或接种疫苗)。我们还收集了接种第二剂COVID-19疫苗约5个月后的人的血液样本(其中大多数人之前没有SARS-CoV-2感染)。我们测量了他们对SARS-CoV-2的体液反应，根据BMI大于或小于25 kg m -2对个体进行分组。研究结果表明，考虑到年龄和性别差异，BMI增加(≥25 kg m−2)与SARS-CoV-2感染后抗体反应降低有关。感染后3个月，BMI升高与抗体滴度降低相关。在感染后13个月，BMI升高与抗体贪婪度降低和尖峰阳性B细胞百分比降低相关。相比之下，在二次疫苗接种后5个月，BMI≥25 kg m -2与对SARS-CoV-2的体液免疫之间没有显著关联。综上所述，这些数据表明，BMI升高与对SARS-CoV-2感染的体液免疫反应受损有关。BMI≥25 kg m−2的个体感染诱导免疫功能受损，表明需要额外的动力接种疫苗，而不是依赖于感染诱导免疫。
{"title":"Elevated BMI reduces the humoral response to SARS-CoV-2 infection","authors":"Marcus ZW Tong, Julian DJ Sng, Meagan Carney, Lucy Cooper, Samuel Brown, Katie E Lineburg, Keng Yih Chew, Neve Collins, Kirsten Ignacio, Megan Airey, Lucy Burr, Briony A Joyce, Dhilshan Jayasinghe, Christopher LD McMillan, David A Muller, Anurag Adhikari, Linda A Gallo, Emily S Dorey, Helen L Barrett, Stephanie Gras, Corey Smith, Kim Good-Jacobson, Kirsty R Short","doi":"10.1002/cti2.1476","DOIUrl":"https://doi.org/10.1002/cti2.1476","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Class III obesity (body mass index [BMI] ≥ 40 kg m<sup>−2</sup>) significantly impairs the immune response to SARS-CoV-2 vaccination. However, the effect of an elevated BMI (≥ 25 kg m<sup>−2</sup>) on humoral immunity to SARS-CoV-2 infection and COVID-19 vaccination remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We collected blood samples from people who recovered from SARS-CoV-2 infection approximately 3 and 13 months of post-infection (noting that these individuals were not exposed to SARS-CoV-2 or vaccinated in the interim). We also collected blood samples from people approximately 5 months of post-second dose COVID-19 vaccination (the majority of whom did not have a prior SARS-CoV-2 infection). We measured their humoral responses to SARS-CoV-2, grouping individuals based on a BMI greater or less than 25 kg m<sup>−2</sup>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here, we show that an increased BMI (≥ 25 kg m<sup>−2</sup>), when accounting for age and sex differences, is associated with reduced antibody responses after SARS-CoV-2 infection. At 3 months of post-infection, an elevated BMI was associated with reduced antibody titres. At 13 months of post-infection, an elevated BMI was associated with reduced antibody avidity and a reduced percentage of spike-positive B cells. In contrast, no significant association was noted between a BMI ≥ 25 kg m<sup>−2</sup> and humoral immunity to SARS-CoV-2 at 5 months of post-secondary vaccination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Taken together, these data showed that elevated BMI is associated with an impaired humoral immune response to SARS-CoV-2 infection. The impairment of infection-induced immunity in individuals with a BMI ≥ 25 kg m<sup>−2</sup> suggests an added impetus for vaccination rather than relying on infection-induced immunity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 12","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1476","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138480933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samuel E Norton, Tiffany Khong, Malarmathy Ramachandran, Andrew J Highton, Kirsten A Ward-Hartstonge, Jake Shortt, Andrew Spencer, Roslyn A Kemp
Objectives
Lenalidomide (LEN) is used to treat multiple myeloma (MM) and shows in vitro synergy with KappaMab (KM), a chimeric antibody specific for Kappa Myeloma antigen, an antigen exclusively expressed on the surface of kappa-restricted MM cells. Lenalidomide, dexamethasone (DEX) and KM control MM via multiple immunomodulatory mechanisms; however, there are several additional effects of the drug combination on immune cells. Lenalidomide can increase T cell and NKT cell cytotoxicity and dendritic cell (DC) activation in vitro. We investigated the immune cell populations in bone marrow of patients treated with KM, LEN and low-dose DEX in kappa-restricted relapsed/refractory MM ex vivo and assessed association of those changes with patient outcome.
Methods
A cohort (n = 40) of patients with kappa-restricted relapsed/refractory MM, treated with KM, LEN and low-dose DEX, was analysed using a mass cytometry panel that allowed identification of immune cell subsets. Clustering analyses were used to determine significant changes in immune cell populations at time periods after treatment.
Results
We found changes in five DC and 17 T-cell populations throughout treatment. We showed an increase in activated conventional DC populations, a decrease in immature/precursor DC populations, a decrease in activated CD4 T cells and an increase in effector-memory CD4 T cells and effector CD8 T cells, indicating an activated immune response.
Conclusion
These data characterise the effects of LEN, DEX, and KM treatment on non-target immune cells in MM. Treatment may support destruction of MM cells by both direct action and indirect mechanisms via immune cells.
{"title":"Changes in immune cell populations following KappaMab, lenalidomide and low-dose dexamethasone treatment in multiple myeloma","authors":"Samuel E Norton, Tiffany Khong, Malarmathy Ramachandran, Andrew J Highton, Kirsten A Ward-Hartstonge, Jake Shortt, Andrew Spencer, Roslyn A Kemp","doi":"10.1002/cti2.1478","DOIUrl":"10.1002/cti2.1478","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Lenalidomide (LEN) is used to treat multiple myeloma (MM) and shows <i>in vitro</i> synergy with KappaMab (KM), a chimeric antibody specific for Kappa Myeloma antigen, an antigen exclusively expressed on the surface of kappa-restricted MM cells. Lenalidomide, dexamethasone (DEX) and KM control MM <i>via</i> multiple immunomodulatory mechanisms; however, there are several additional effects of the drug combination on immune cells. Lenalidomide can increase T cell and NKT cell cytotoxicity and dendritic cell (DC) activation <i>in vitro</i>. We investigated the immune cell populations in bone marrow of patients treated with KM, LEN and low-dose DEX in kappa-restricted relapsed/refractory MM <i>ex vivo</i> and assessed association of those changes with patient outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cohort (<i>n</i> = 40) of patients with kappa-restricted relapsed/refractory MM, treated with KM, LEN and low-dose DEX, was analysed using a mass cytometry panel that allowed identification of immune cell subsets. Clustering analyses were used to determine significant changes in immune cell populations at time periods after treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found changes in five DC and 17 T-cell populations throughout treatment. We showed an increase in activated conventional DC populations, a decrease in immature/precursor DC populations, a decrease in activated CD4 T cells and an increase in effector-memory CD4 T cells and effector CD8 T cells, indicating an activated immune response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These data characterise the effects of LEN, DEX, and KM treatment on non-target immune cells in MM. Treatment may support destruction of MM cells by both direct action and indirect mechanisms <i>via</i> immune cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 12","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138456636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immunoglobulin G4 (IgG4)-related disease is a chronic fibroinflammatory disease mediated by immune disorders. Given the challenging clinical diagnosis and treatment, knowledge of the pathogenesis of IgG4-related disease is important. The typical elevation of serum IgG4 concentrations and infiltration of IgG4-positive plasma cells in the involved tissues indicate the involvement of B lymphocytes in the pathogenesis of IgG4-related disease. Mass production of autoantibodies reflects abnormal activation of B cells, which causes tissue damage. Circulating plasmablasts are recently discovered markers that correlate with serum IgG4 concentration, the extent of organ involvement and disease activity. B-cell depletion therapy is an emerging curative strategy that can significantly alleviate clinical manifestations and achieve remission in patients with IgG4-related disease. These findings highlight the potential role of B cells in IgG4-related disease. In this review, we discuss the pathogenic impact of B lymphocytes on IgG4-related disease and describe novel therapies targeting B cells.
{"title":"The spectrum of B cells in the pathogenesis, diagnosis and therapeutic applications of immunoglobulin G4-related disease","authors":"Qiyuan Hao, Meng Sun, Yanying Liu","doi":"10.1002/cti2.1477","DOIUrl":"https://doi.org/10.1002/cti2.1477","url":null,"abstract":"<p>Immunoglobulin G4 (IgG4)-related disease is a chronic fibroinflammatory disease mediated by immune disorders. Given the challenging clinical diagnosis and treatment, knowledge of the pathogenesis of IgG4-related disease is important. The typical elevation of serum IgG4 concentrations and infiltration of IgG4-positive plasma cells in the involved tissues indicate the involvement of B lymphocytes in the pathogenesis of IgG4-related disease. Mass production of autoantibodies reflects abnormal activation of B cells, which causes tissue damage. Circulating plasmablasts are recently discovered markers that correlate with serum IgG4 concentration, the extent of organ involvement and disease activity. B-cell depletion therapy is an emerging curative strategy that can significantly alleviate clinical manifestations and achieve remission in patients with IgG4-related disease. These findings highlight the potential role of B cells in IgG4-related disease. In this review, we discuss the pathogenic impact of B lymphocytes on IgG4-related disease and describe novel therapies targeting B cells.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 12","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1477","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138454728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lauren Stern, Helen M McGuire, Selmir Avdic, Emily Blyth, David Gottlieb, Ellis Patrick, Allison Abendroth, Barry Slobedman
Objectives
Human cytomegalovirus (HCMV) reactivation is the leading viral complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Understanding of circulating cytokine/chemokine patterns which accompany HCMV reactivation and correlate with HCMV DNAemia magnitude is limited. We aimed to characterise plasma cytokine/chemokine profiles in 36 allo-HSCT patients (21 with HCMV reactivation and 15 without HCMV reactivation) at four time-points in the first 100-day post-transplant.
Methods
The concentrations of 31 cytokines/chemokines in plasma samples were analysed using a multiplex bead-based immunoassay. Cytokine/chemokine concentrations were compared in patients with high-level HCMV DNAemia, low-level HCMV DNAemia or no HCMV reactivation, and correlated with immune cell frequencies measured using mass cytometry.
Results
Increased plasma levels of T helper 1-type cytokines/chemokines (TNF, IL-18, IP-10, MIG) were detected in patients with HCMV reactivation at the peak of HCMV DNAemia, relative to non-reactivators. Stem cell factor (SCF) levels were significantly higher before the detection of HCMV reactivation in patients who went on to develop high-level HCMV DNAemia (810–52 740 copies/mL) vs. low-level HCMV DNAemia (< 250 copies/mL). High-level HCMV reactivators, but not low-level reactivators, developed an elevated inflammatory cytokine/chemokine profile (MIP-1α, MIP-1β, TNF, LT-α, IL-13, IL-9, SCF, HGF) at the peak of reactivation. Plasma cytokine concentrations displayed unique correlations with circulating immune cell frequencies in patients with HCMV reactivation.
Conclusion
This study identifies distinct circulating cytokine/chemokine signatures associated with the magnitude of HCMV DNAemia and the progression of HCMV reactivation after allo-HSCT, providing important insight into immune recovery patterns associated with HCMV reactivation and viral control.
{"title":"Circulating cytokine and chemokine patterns associated with cytomegalovirus reactivation after stem cell transplantation","authors":"Lauren Stern, Helen M McGuire, Selmir Avdic, Emily Blyth, David Gottlieb, Ellis Patrick, Allison Abendroth, Barry Slobedman","doi":"10.1002/cti2.1473","DOIUrl":"https://doi.org/10.1002/cti2.1473","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Human cytomegalovirus (HCMV) reactivation is the leading viral complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Understanding of circulating cytokine/chemokine patterns which accompany HCMV reactivation and correlate with HCMV DNAemia magnitude is limited. We aimed to characterise plasma cytokine/chemokine profiles in 36 allo-HSCT patients (21 with HCMV reactivation and 15 without HCMV reactivation) at four time-points in the first 100-day post-transplant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The concentrations of 31 cytokines/chemokines in plasma samples were analysed using a multiplex bead-based immunoassay. Cytokine/chemokine concentrations were compared in patients with high-level HCMV DNAemia, low-level HCMV DNAemia or no HCMV reactivation, and correlated with immune cell frequencies measured using mass cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Increased plasma levels of T helper 1-type cytokines/chemokines (TNF, IL-18, IP-10, MIG) were detected in patients with HCMV reactivation at the peak of HCMV DNAemia, relative to non-reactivators. Stem cell factor (SCF) levels were significantly higher before the detection of HCMV reactivation in patients who went on to develop high-level HCMV DNAemia (810–52 740 copies/mL) <i>vs.</i> low-level HCMV DNAemia (< 250 copies/mL). High-level HCMV reactivators, but not low-level reactivators, developed an elevated inflammatory cytokine/chemokine profile (MIP-1α, MIP-1β, TNF, LT-α, IL-13, IL-9, SCF, HGF) at the peak of reactivation. Plasma cytokine concentrations displayed unique correlations with circulating immune cell frequencies in patients with HCMV reactivation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study identifies distinct circulating cytokine/chemokine signatures associated with the magnitude of HCMV DNAemia and the progression of HCMV reactivation after allo-HSCT, providing important insight into immune recovery patterns associated with HCMV reactivation and viral control.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 12","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138454727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoyan Deng, Pierre Gantner, Julia Forestell, Amélie Pagliuzza, Elsa Brunet-Ratnasingham, Madeleine Durand, Daniel E Kaufmann, Nicolas Chomont, Morgan Craig
Objectives
Identifying biomarkers causing differential SARS-CoV-2 infection kinetics associated with severe COVID-19 is fundamental for effective diagnostics and therapeutic planning.
Methods
In this work, we applied mathematical modelling to investigate the relationships between patient characteristics, plasma SARS-CoV-2 RNA dynamics and COVID-19 severity. Using a straightforward mathematical model of within-host viral kinetics, we estimated key model parameters from serial plasma viral RNA (vRNA) samples from 256 hospitalised COVID-19+ patients.
Results
Our model predicted that clearance rates distinguish key differences in plasma vRNA kinetics and severe COVID-19. Moreover, our analyses revealed a strong correlation between plasma vRNA kinetics and plasma receptor for advanced glycation end products (RAGE) concentrations (a plasma biomarker of lung damage), collected in parallel to plasma vRNA from patients in our cohort, suggesting that RAGE can substitute for viral plasma shedding dynamics to prospectively classify seriously ill patients.
Conclusion
Overall, our study identifies factors of COVID-19 severity, supports interventions to accelerate viral clearance and underlines the importance of mathematical modelling to better understand COVID-19.
{"title":"Plasma SARS-CoV-2 RNA elimination and RAGE kinetics distinguish COVID-19 severity","authors":"Xiaoyan Deng, Pierre Gantner, Julia Forestell, Amélie Pagliuzza, Elsa Brunet-Ratnasingham, Madeleine Durand, Daniel E Kaufmann, Nicolas Chomont, Morgan Craig","doi":"10.1002/cti2.1468","DOIUrl":"https://doi.org/10.1002/cti2.1468","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Identifying biomarkers causing differential SARS-CoV-2 infection kinetics associated with severe COVID-19 is fundamental for effective diagnostics and therapeutic planning.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this work, we applied mathematical modelling to investigate the relationships between patient characteristics, plasma SARS-CoV-2 RNA dynamics and COVID-19 severity. Using a straightforward mathematical model of within-host viral kinetics, we estimated key model parameters from serial plasma viral RNA (vRNA) samples from 256 hospitalised COVID-19<sup>+</sup> patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our model predicted that clearance rates distinguish key differences in plasma vRNA kinetics and severe COVID-19. Moreover, our analyses revealed a strong correlation between plasma vRNA kinetics and plasma receptor for advanced glycation end products (RAGE) concentrations (a plasma biomarker of lung damage), collected in parallel to plasma vRNA from patients in our cohort, suggesting that RAGE can substitute for viral plasma shedding dynamics to prospectively classify seriously ill patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall, our study identifies factors of COVID-19 severity, supports interventions to accelerate viral clearance and underlines the importance of mathematical modelling to better understand COVID-19.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 11","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1468","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138432502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyunjung Min, Laura A Valente, Li Xu, Shane M O'Neil, Lauren R Begg, Joanne Kurtzberg, Anthony J Filiano
<div> <section> <h3> Objectives</h3> <p>Thymus implantation is a recently FDA-approved therapy for congenital athymia. Patients receiving thymus implantation develop a functional but incomplete T cell compartment. Our objective was to develop a mouse model to study clinical thymus implantation in congenital athymia and to optimise implantation procedures to maximise T cell education and expansion of naïve T cells.</p> </section> <section> <h3> Methods</h3> <p>Using <i>Foxn1</i><sup>nu</sup> athymic mice as recipients, we tested MHC-matched and -mismatched donor thymi that were implanted as fresh tissue or cultured to remove donor T cells. We first implanted thymus under the kidney capsule and then optimised intramuscular implantation. Using competitive adoptive transfer assays, we investigated whether the failure of newly developed T cells to expand into a complete T cell compartment was because of intrinsic deficits or whether there were deficits in engaging MHC molecules in the periphery. Finally, we tested whether recombinant IL-7 would promote the expansion of host naïve T cells educated by the implanted thymus.</p> </section> <section> <h3> Results</h3> <p>We determined that thymus implants in <i>Foxn1</i><sup>nu</sup> athymic mice mimic many aspects of clinical thymus implants in patients with congenital athymia. When we implanted cultured, MHC-mismatched donor thymus into <i>Foxn1</i><sup>nu</sup> athymic mice, mice developed a limited T cell compartment with notably underdeveloped naïve populations and overrepresented memory-like T cells. Newly generated T cells were predominantly educated by MHC molecules expressed by the donor thymus, thus potentially undergoing another round of selection once in the peripheral circulation. Using competitive adoptive transfer assays, we compared expansion rates of T cells educated on donor thymus <i>versus</i> T cells educated during typical thymopoiesis in MHC-matched and -mismatched environments. Once in the circulation, regardless of the MHC haplotypes, T cells educated on a donor thymus underwent abnormal expansion with initially more robust proliferation coupled with greater cell death, resembling IL-7 independent spontaneous expansion. Treating implanted mice with recombinant interleukin (IL-7) promoted homeostatic expansion that improved T cell development, expanded the T cell receptor repertoire, and normalised the naïve T cell compartment.</p> </section> <section> <h3> Conclusion</h3> <p>We conclude that implanting cultured thymus into the muscle of <i>Foxn1</i><sup>nu</sup> athymic mice is an ap
{"title":"Improving thymus implantation for congenital athymia with interleukin-7","authors":"Hyunjung Min, Laura A Valente, Li Xu, Shane M O'Neil, Lauren R Begg, Joanne Kurtzberg, Anthony J Filiano","doi":"10.1002/cti2.1475","DOIUrl":"https://doi.org/10.1002/cti2.1475","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Thymus implantation is a recently FDA-approved therapy for congenital athymia. Patients receiving thymus implantation develop a functional but incomplete T cell compartment. Our objective was to develop a mouse model to study clinical thymus implantation in congenital athymia and to optimise implantation procedures to maximise T cell education and expansion of naïve T cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using <i>Foxn1</i><sup>nu</sup> athymic mice as recipients, we tested MHC-matched and -mismatched donor thymi that were implanted as fresh tissue or cultured to remove donor T cells. We first implanted thymus under the kidney capsule and then optimised intramuscular implantation. Using competitive adoptive transfer assays, we investigated whether the failure of newly developed T cells to expand into a complete T cell compartment was because of intrinsic deficits or whether there were deficits in engaging MHC molecules in the periphery. Finally, we tested whether recombinant IL-7 would promote the expansion of host naïve T cells educated by the implanted thymus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We determined that thymus implants in <i>Foxn1</i><sup>nu</sup> athymic mice mimic many aspects of clinical thymus implants in patients with congenital athymia. When we implanted cultured, MHC-mismatched donor thymus into <i>Foxn1</i><sup>nu</sup> athymic mice, mice developed a limited T cell compartment with notably underdeveloped naïve populations and overrepresented memory-like T cells. Newly generated T cells were predominantly educated by MHC molecules expressed by the donor thymus, thus potentially undergoing another round of selection once in the peripheral circulation. Using competitive adoptive transfer assays, we compared expansion rates of T cells educated on donor thymus <i>versus</i> T cells educated during typical thymopoiesis in MHC-matched and -mismatched environments. Once in the circulation, regardless of the MHC haplotypes, T cells educated on a donor thymus underwent abnormal expansion with initially more robust proliferation coupled with greater cell death, resembling IL-7 independent spontaneous expansion. Treating implanted mice with recombinant interleukin (IL-7) promoted homeostatic expansion that improved T cell development, expanded the T cell receptor repertoire, and normalised the naïve T cell compartment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We conclude that implanting cultured thymus into the muscle of <i>Foxn1</i><sup>nu</sup> athymic mice is an ap","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 11","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1475","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138431978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ebene R Haycroft, Timon Damelang, Ester Lopez, Mark A Rodgers, Bruce D Wines, Mark Hogarth, Cassaundra L Ameel, Stephen J Kent, Charles A Scanga, Shelby L O'Connor, Amy W Chung
Objectives
Tuberculosis (TB) remains a substantial cause of morbidity and mortality among people living with human immunodeficiency virus (HIV) worldwide. However, the immunological mechanisms associated with the enhanced susceptibility among HIV-positive individuals remain largely unknown.
Methods
Here, we used a simian immunodeficiency virus (SIV)/TB-coinfection Mauritian cynomolgus macaque (MCM) model to examine humoral responses from the plasma of SIV-negative (n = 8) and SIV-positive (n = 7) MCM 8-week postinfection with Mycobacterium tuberculosis (Mtb).
Results
Antibody responses to Mtb were impaired during SIV coinfection. Elevated inflammatory bulk IgG antibody glycosylation patterns were observed in coinfected macaques early at 8-week post-Mtb infection, including increased agalactosylation (G0) and reduced di-galactosylation (G2), which correlated with endpoint Mtb bacterial burden and gross pathology scores, as well as the time-to-necropsy.
Conclusion
These studies suggest that humoral immunity may contribute to control of TB disease and support growing literature that highlights antibody Fc glycosylation as a biomarker of TB disease progression.
{"title":"Antibody glycosylation correlates with disease progression in SIV-Mycobacterium tuberculosis coinfected cynomolgus macaques","authors":"Ebene R Haycroft, Timon Damelang, Ester Lopez, Mark A Rodgers, Bruce D Wines, Mark Hogarth, Cassaundra L Ameel, Stephen J Kent, Charles A Scanga, Shelby L O'Connor, Amy W Chung","doi":"10.1002/cti2.1474","DOIUrl":"https://doi.org/10.1002/cti2.1474","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Tuberculosis (TB) remains a substantial cause of morbidity and mortality among people living with human immunodeficiency virus (HIV) worldwide. However, the immunological mechanisms associated with the enhanced susceptibility among HIV-positive individuals remain largely unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we used a simian immunodeficiency virus (SIV)/TB-coinfection Mauritian cynomolgus macaque (MCM) model to examine humoral responses from the plasma of SIV-negative (<i>n</i> = 8) and SIV-positive (<i>n</i> = 7) MCM 8-week postinfection with <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Antibody responses to <i>Mtb</i> were impaired during SIV coinfection. Elevated inflammatory bulk IgG antibody glycosylation patterns were observed in coinfected macaques early at 8-week post-<i>Mtb</i> infection, including increased agalactosylation (G0) and reduced di-galactosylation (G2), which correlated with endpoint <i>Mtb</i> bacterial burden and gross pathology scores, as well as the time-to-necropsy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These studies suggest that humoral immunity may contribute to control of TB disease and support growing literature that highlights antibody Fc glycosylation as a biomarker of TB disease progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 11","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1474","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138432372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonas Saal, Jörg Ellinger, Manuel Ritter, Peter Brossart, Michael Hölzel, Niklas Klümper, Tobias Bald
Objectives
Reliable predictive biomarkers for response to immune checkpoint inhibition (ICI) are lacking. Pretreatment serum albumin, a known prognostic and predictive factor in ICI-treated patients, has been proposed as a potential pharmacokinetic surrogate marker for anti-PD1/PD-L1 antibodies, as it shares a homeostatic pathway with IgG. However, this hypothesis is currently based on theoretical considerations and limited evidence from retrospective data. Therefore, we comprehensively investigated the prognostic and predictive value of pretreatment albumin and its relationship with anti-PD-L1 IgG levels.
Methods
We analysed pretreatment albumin and atezolizumab serum levels and clinical response in four trials (IMvigor210, IMvigor211, IMmotion151 and OAK) of patients with metastatic lung-, renal- or urothelial cancer who received atezolizumab alone or in combination.
Results
A total of 3391 patients were analysed. Correlation between serum albumin and atezolizumab levels was weak (Pearson's coefficient 0.23). We found a strong prognostic value for pretreatment serum albumin across all trials. Both atezolizumab serum levels and serum albumin were independently correlated with overall survival. Importantly, in the three randomised phase III clinical trials, the survival benefit for immunotherapy compared with the active comparator arm was limited to patients with pretreatment serum albumin > 35 g L−1.
Conclusion
Our data do not support the hypothesis that albumin serves as a surrogate for atezolizumab pharmacokinetics. However, we show that albumin on its own exerts strong prognostic value for patients treated with immunotherapy. As benefit from immunotherapy was limited to patients with normal/elevated serum albumin levels, baseline albumin could potentially be used as a predictive marker for immune checkpoint inhibition.
{"title":"Pretreatment albumin is a prognostic and predictive biomarker for response to atezolizumab across solid tumors","authors":"Jonas Saal, Jörg Ellinger, Manuel Ritter, Peter Brossart, Michael Hölzel, Niklas Klümper, Tobias Bald","doi":"10.1002/cti2.1472","DOIUrl":"10.1002/cti2.1472","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Reliable predictive biomarkers for response to immune checkpoint inhibition (ICI) are lacking. Pretreatment serum albumin, a known prognostic and predictive factor in ICI-treated patients, has been proposed as a potential pharmacokinetic surrogate marker for anti-PD1/PD-L1 antibodies, as it shares a homeostatic pathway with IgG. However, this hypothesis is currently based on theoretical considerations and limited evidence from retrospective data. Therefore, we comprehensively investigated the prognostic and predictive value of pretreatment albumin and its relationship with anti-PD-L1 IgG levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed pretreatment albumin and atezolizumab serum levels and clinical response in four trials (IMvigor210, IMvigor211, IMmotion151 and OAK) of patients with metastatic lung-, renal- or urothelial cancer who received atezolizumab alone or in combination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 3391 patients were analysed. Correlation between serum albumin and atezolizumab levels was weak (Pearson's coefficient 0.23). We found a strong prognostic value for pretreatment serum albumin across all trials. Both atezolizumab serum levels and serum albumin were independently correlated with overall survival. Importantly, in the three randomised phase III clinical trials, the survival benefit for immunotherapy compared with the active comparator arm was limited to patients with pretreatment serum albumin > 35 g L<sup>−1</sup>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data do not support the hypothesis that albumin serves as a surrogate for atezolizumab pharmacokinetics. However, we show that albumin on its own exerts strong prognostic value for patients treated with immunotherapy. As benefit from immunotherapy was limited to patients with normal/elevated serum albumin levels, baseline albumin could potentially be used as a predictive marker for immune checkpoint inhibition.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 11","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10632074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72012782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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