Pub Date : 2026-03-11DOI: 10.1016/j.imbio.2026.153173
Yujie Cao, Xi Liu, Ruijing Zhao, Yang Li, Hangyu Gao, Yang Yang, Jun Yu, Jianying Li
Introduction: In the context of tumor diseases, aberrant splicing has become a potential source for targeted treatment. In this work, we discovered a 147-bp splicing anomaly in the downstream target gene BTC, which is regulated by the HNRNPDL gene in non-small cell lung cancer. The biological significance and therapeutic relevance of this splicing regulation remain unclear.
Methods: RNA sequencing (RNA-seq) was used to carefully screen for differential genes downstream of HNRNPDL that were transfected into NSCLC cell lines using lentivirus-mediated short hairpin RNA (shRNA). As a result, key splicing events linked to NSCLC were identified. Additionally, NSCLC cell lines received shRNA plasmids that targeted different spliceosomes of HNRNPDL and BTC, which sparked a series of in vitro tests intended to clarify their biological functions.
Results: There was an up-regulation of the HNRNPDL expression profile. Due to exon 4 aberrancy, the RNA-seq study concurrently produced two transcripts, namely exon 4 (BTC-L) and exon 4 skipping transcripts (BTC-S). In contrast to normal bronchial cells (BEAS-2B), BTC-L and BTC-S were both significantly up-regulated in NSCLC cell lines. Experiments conducted in vitro clearly demonstrated that both BTC-L and BTC-S could promote the migration and proliferation of non-small cell lung cancer cells and inhibit their apoptosis, showing comparable oncogenic phenotypes in vitro.
Conclusions: Our findings suggest that HNRNPDL may contribute to NSCLC progression by regulating BTC alternative splicing.
{"title":"HNRNPDL facilitates the advancement of non-small cell lung carcinoma via modulating the alternative splicing of the BTC gene.","authors":"Yujie Cao, Xi Liu, Ruijing Zhao, Yang Li, Hangyu Gao, Yang Yang, Jun Yu, Jianying Li","doi":"10.1016/j.imbio.2026.153173","DOIUrl":"https://doi.org/10.1016/j.imbio.2026.153173","url":null,"abstract":"<p><strong>Introduction: </strong>In the context of tumor diseases, aberrant splicing has become a potential source for targeted treatment. In this work, we discovered a 147-bp splicing anomaly in the downstream target gene BTC, which is regulated by the HNRNPDL gene in non-small cell lung cancer. The biological significance and therapeutic relevance of this splicing regulation remain unclear.</p><p><strong>Methods: </strong>RNA sequencing (RNA-seq) was used to carefully screen for differential genes downstream of HNRNPDL that were transfected into NSCLC cell lines using lentivirus-mediated short hairpin RNA (shRNA). As a result, key splicing events linked to NSCLC were identified. Additionally, NSCLC cell lines received shRNA plasmids that targeted different spliceosomes of HNRNPDL and BTC, which sparked a series of in vitro tests intended to clarify their biological functions.</p><p><strong>Results: </strong>There was an up-regulation of the HNRNPDL expression profile. Due to exon 4 aberrancy, the RNA-seq study concurrently produced two transcripts, namely exon 4 (BTC-L) and exon 4 skipping transcripts (BTC-S). In contrast to normal bronchial cells (BEAS-2B), BTC-L and BTC-S were both significantly up-regulated in NSCLC cell lines. Experiments conducted in vitro clearly demonstrated that both BTC-L and BTC-S could promote the migration and proliferation of non-small cell lung cancer cells and inhibit their apoptosis, showing comparable oncogenic phenotypes in vitro.</p><p><strong>Conclusions: </strong>Our findings suggest that HNRNPDL may contribute to NSCLC progression by regulating BTC alternative splicing.</p>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"153173"},"PeriodicalIF":2.3,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-03-06DOI: 10.1016/j.imbio.2026.153172
Miao Liu , Shuping Liu , Wenjie Xie , Guang Li , Tao Deng
Background
Clostridium butyricum (CB), a butyrate-producing probiotic, exhibits antitumor potential in colorectal cancer (CRC). This study investigated the direct effects and mechanisms of CB-secreted metabolites on CRC cells.
Methods
HT-29 cells were treated with serial dilutions (5–40%) of sterile-filtered CB supernatant (CBS), using E. coli DH5α supernatant as control. Cell viability and proliferation were assessed by CCK-8 and Ki-67 immunofluorescence. Apoptosis was evaluated by Annexin V/PI flow cytometry. Mitochondrial membrane potential (ΔΨm) was monitored via JC-1 staining. Apoptosis-related and NF-κB pathway proteins were analyzed by Western blot.
Results
The CBS notably suppressed HT-29 cell viability and proliferation as concentration and treatment duration increased, with an IC₅₀ of 18.84% (95% CI: 16.2% to 21.5%) at 48 h. CBS exposure markedly increased apoptotic cell proportion. Mechanistically, CBS induced ΔΨm loss, cytosolic cytochrome c translocation, and activation of caspase-9 and -3. Concurrently, CBS inhibited NF-κB pathway activation, downregulated Bcl-2, and upregulated Bax.
Conclusion
CB culture supernatant inhibits growth and induces apoptosis in HT-29 cells through mitochondrial dysfunction and NF-κB suppression.
{"title":"Cell-free supernatant of Clostridium butyricum induces mitochondrial apoptosis and suppresses NF-κB pathway in colorectal cancer cells","authors":"Miao Liu , Shuping Liu , Wenjie Xie , Guang Li , Tao Deng","doi":"10.1016/j.imbio.2026.153172","DOIUrl":"10.1016/j.imbio.2026.153172","url":null,"abstract":"<div><h3>Background</h3><div><em>Clostridium butyricum</em> (CB), a butyrate-producing probiotic, exhibits antitumor potential in colorectal cancer (CRC). This study investigated the direct effects and mechanisms of CB-secreted metabolites on CRC cells.</div></div><div><h3>Methods</h3><div>HT-29 cells were treated with serial dilutions (5–40%) of sterile-filtered CB supernatant (CBS), using <em>E. coli</em> DH5α supernatant as control. Cell viability and proliferation were assessed by CCK-8 and Ki-67 immunofluorescence. Apoptosis was evaluated by Annexin V/PI flow cytometry. Mitochondrial membrane potential (ΔΨm) was monitored via JC-1 staining. Apoptosis-related and NF-κB pathway proteins were analyzed by Western blot.</div></div><div><h3>Results</h3><div>The CBS notably suppressed HT-29 cell viability and proliferation as concentration and treatment duration increased, with an IC₅₀ of 18.84% (95% CI: 16.2% to 21.5%) at 48 h. CBS exposure markedly increased apoptotic cell proportion. Mechanistically, CBS induced ΔΨm loss, cytosolic cytochrome <em>c</em> translocation, and activation of caspase-9 and -3. Concurrently, CBS inhibited NF-κB pathway activation, downregulated Bcl-2, and upregulated Bax.</div></div><div><h3>Conclusion</h3><div>CB culture supernatant inhibits growth and induces apoptosis in HT-29 cells through mitochondrial dysfunction and NF-κB suppression.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 2","pages":"Article 153172"},"PeriodicalIF":2.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147448670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-18DOI: 10.1016/j.imbio.2026.153165
Hong Zhang , Ming Liu , Tongbao Feng , Ping Zhang , Yan Wang
Programmed Death-Ligand 1 (PD-L1) has been proven to mediate various mechanisms to induce T-cell dysfunction in influenza A virus infection. However, whether PD-L1 similarly contributes to inflammatory responses during influenza B virus (IBV) infection remains unknown. Here we investigated PD-L1 expression patterns during acute IBV infection. A total of 24 IBV-infected patients and 33 healthy controls were recruited and assigned to three age subgroups. Using flow cytometry, we assessed PD-L1 expression on circulating leukocytes and measured the concentrations of plasma cytokines. Our findings demonstrated that IBV infection induced PD-L1 expression on human dendritic cells, T-cells and monocytes. Additionally, IL-2, IL-4, IL-6, IL-10, and TNF concentrations elevated significantly, indicating the occurrence of robust inflammatory responses. Notably, age did not influence PD-L1 expression on peripheral immune cells across the three age subgroups. These results reveal that IBV infection involves the expression of PD-L1 on key immune cell populations, and PD-L1 may serve as a target in the design of new therapeutic strategies for IBV.
{"title":"Programmed death-ligand 1 correlates with acute influenza B virus infection","authors":"Hong Zhang , Ming Liu , Tongbao Feng , Ping Zhang , Yan Wang","doi":"10.1016/j.imbio.2026.153165","DOIUrl":"10.1016/j.imbio.2026.153165","url":null,"abstract":"<div><div>Programmed Death-Ligand 1 (PD-L1) has been proven to mediate various mechanisms to induce T-cell dysfunction in influenza A virus infection. However, whether PD-L1 similarly contributes to inflammatory responses during influenza B virus (IBV) infection remains unknown. Here we investigated PD-L1 expression patterns during acute IBV infection. A total of 24 IBV-infected patients and 33 healthy controls were recruited and assigned to three age subgroups. Using flow cytometry, we assessed PD-L1 expression on circulating leukocytes and measured the concentrations of plasma cytokines. Our findings demonstrated that IBV infection induced PD-L1 expression on human dendritic cells, T-cells and monocytes. Additionally, IL-2, IL-4, IL-6, IL-10, and TNF concentrations elevated significantly, indicating the occurrence of robust inflammatory responses. Notably, age did not influence PD-L1 expression on peripheral immune cells across the three age subgroups. These results reveal that IBV infection involves the expression of PD-L1 on key immune cell populations, and PD-L1 may serve as a target in the design of new therapeutic strategies for IBV.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 2","pages":"Article 153165"},"PeriodicalIF":2.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147270833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-21DOI: 10.1016/j.imbio.2026.153167
Jiao Yu , Yang Zhang , Qing Wang , Lei An , Yuyan Guo , Hongtao Ren
Background
Radiation enteritis (RE), an intestinal complication due to abdominal or pelvic radiotherapy, severely impacts patients' life and health. Paeoniflorin (PF), a water-soluble monoterpene glycoside, is reported to relieve RE, but its molecular mechanism needs further exploration. Thus, this study aims to clarify the molecular mechanism underlying PF's effect on RE.
Methods
An in vitro ionizing radiation (IR)-induced cell model was constructed. Subsequently, CCK-8, EdU, flow cytometry and relevant kits were applied to examine cellular behaviors and ferroptosis. Protein and mRNA expression levels were assessed via Western blot and qRT-PCR. Bioinformatics tools, ChIP, and dual-luciferase reporter assays were employed to ascertain the regulatory relationship between YY1 and ACSL4. Furthermore, the RE mouse model was established for in vivo experiments.
Results
PF inhibited ionizing radiation (IR)-induced injury and ferroptosis in mouse intestinal epithelial cells (IEC-6). The inhibitory effect of PF was mediated by inhibiting ACSL4. YY1 activated the transcription of ACSL4 to promote its expression. Moreover, ACSL4 upregulation abrogated the protective effect of silencing YY1 on cell damage induced by IR. PF curbed YY1 expression, thereby suppressing the damage to IEC-6 cells induced by IR. Besides, PF constrained ACSL4 and the progression of radiation enteritis in vivo.
Conclusion
PF alleviated IR-induced damage and ferroptosis of IEC-6 cells by targeting the YY1/ACSL4 axis, providing a novel mechanistic basis for its application in RE treatment.
{"title":"Paeoniflorin protects against radiation enteritis by suppressing YY1/ACSL4 axis to attenuate murine intestinal epithelial injury and ferroptosis","authors":"Jiao Yu , Yang Zhang , Qing Wang , Lei An , Yuyan Guo , Hongtao Ren","doi":"10.1016/j.imbio.2026.153167","DOIUrl":"10.1016/j.imbio.2026.153167","url":null,"abstract":"<div><h3>Background</h3><div>Radiation enteritis (RE), an intestinal complication due to abdominal or pelvic radiotherapy, severely impacts patients' life and health. Paeoniflorin (PF), a water-soluble monoterpene glycoside, is reported to relieve RE, but its molecular mechanism needs further exploration. Thus, this study aims to clarify the molecular mechanism underlying PF's effect on RE.</div></div><div><h3>Methods</h3><div>An <em>in vitro</em> ionizing radiation (IR)-induced cell model was constructed. Subsequently, CCK-8, EdU, flow cytometry and relevant kits were applied to examine cellular behaviors and ferroptosis. Protein and mRNA expression levels were assessed <em>via</em> Western blot and qRT-PCR. Bioinformatics tools, ChIP, and dual-luciferase reporter assays were employed to ascertain the regulatory relationship between YY1 and ACSL4. Furthermore, the RE mouse model was established for <em>in vivo</em> experiments.</div></div><div><h3>Results</h3><div>PF inhibited ionizing radiation (IR)-induced injury and ferroptosis in mouse intestinal epithelial cells (IEC-6). The inhibitory effect of PF was mediated by inhibiting ACSL4. YY1 activated the transcription of ACSL4 to promote its expression. Moreover, ACSL4 upregulation abrogated the protective effect of silencing YY1 on cell damage induced by IR. PF curbed YY1 expression, thereby suppressing the damage to IEC-6 cells induced by IR. Besides, PF constrained ACSL4 and the progression of radiation enteritis <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>PF alleviated IR-induced damage and ferroptosis of IEC-6 cells by targeting the YY1/ACSL4 axis, providing a novel mechanistic basis for its application in RE treatment.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 2","pages":"Article 153167"},"PeriodicalIF":2.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147448802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-31DOI: 10.1016/j.imbio.2026.153162
Kevin Gonzales, Jessy Condori, Guillermo Fernández , Manuela Verastegui
Background: Neurocysticercosis (NCC) is a parasitic infection of the central nervous system (CNS) caused by the larval form of Taenia solium. This disease provokes an inflammatory response that intensifies when the parasite dies. This study aimed to assess the expression of the cytokines IL-10, IL-1β, and TGF-β in primary astrocyte cultures derived from rat brains at 5 and 14 days in vitro (DIV) following exposure to T. solium cysticercus antigens. Methods: Primary astrocyte cultures obtained from 3-day-old postnatal rats were incubated for 24 h with either Excretory/Secretory (E/S) antigens or Total antigen (Tag), while lipopolysaccharide (LPS) was used as a positive control. Cytokine expression (IL-10, IL-1β, and TGF-β1) was quantified by RT-qPCR. Results: DIV5 culture contains astrocytes and neurons, while in DIV14 only astrocytes were detected. At DIV5, the incubation with E/S products increased the gene expression of IL-10 and IL-1β. Conversely,at DIV14, E/S antigens only augmented IL-10 mRNA levels. Moreover, Tag did not change IL-10, IL-1β, and TGF-β gene expression in both DIV5 and DIV14 cultures. Finally, TGF-β expression remains unchanged after T. solium antigen exposure. Conclusions:T. solium E/S products may differentially modulate astrocyte cytokine responses in a stage-dependent manner. In addition, the Tag obtained from viable cysts does not affect the studied cytokine gene expression. These results underscore the potential role of astrocytes in the neuroinflammatory processes associated with NCC.
{"title":"Differential astrocyte activation by Taenia solium antigens: Specific induction of IL-10 and IL-1β by Excretory/Secretory (ES) products","authors":"Kevin Gonzales, Jessy Condori, Guillermo Fernández , Manuela Verastegui","doi":"10.1016/j.imbio.2026.153162","DOIUrl":"10.1016/j.imbio.2026.153162","url":null,"abstract":"<div><div><strong>Background:</strong> Neurocysticercosis (NCC) is a parasitic infection of the central nervous system (CNS) caused by the larval form of <em>Taenia solium</em>. This disease provokes an inflammatory response that intensifies when the parasite dies. This study aimed to assess the expression of the cytokines IL-10, IL-1β, and TGF-β in primary astrocyte cultures derived from rat brains at 5 and 14 days in vitro (DIV) following exposure to <em>T. solium</em> cysticercus antigens. <strong>Methods:</strong> Primary astrocyte cultures obtained from 3-day-old postnatal rats were incubated for 24 h with either Excretory/Secretory (E/S) antigens or Total antigen (Tag), while lipopolysaccharide (LPS) was used as a positive control. Cytokine expression (IL-10, IL-1β, and TGF-β1) was quantified by RT-qPCR. <strong>Results:</strong> DIV5 culture contains astrocytes and neurons, while in DIV14 only astrocytes were detected. At DIV5, the incubation with E/S products increased the gene expression of IL-10 and IL-1β. Conversely,at DIV14, E/S antigens only augmented IL-10 mRNA levels. Moreover, Tag did not change IL-10, IL-1β, and TGF-β gene expression in both DIV5 and DIV14 cultures. Finally, TGF-β expression remains unchanged after <em>T. solium</em> antigen exposure. <strong>Conclusions:</strong> <em>T. solium</em> E/S products may differentially modulate astrocyte cytokine responses in a stage-dependent manner. In addition, the Tag obtained from viable cysts does not affect the studied cytokine gene expression. These results underscore the potential role of astrocytes in the neuroinflammatory processes associated with NCC.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 2","pages":"Article 153162"},"PeriodicalIF":2.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-02DOI: 10.1016/j.imbio.2026.153163
Bo-Xiang Benjamin Zhang , Hong-Yi Lin , Hoang Yen Tran , Chung-Che Wu , Kai-Yun Chen , Tsung-I Hsu , Chih-Jie Shen
Objective
Hepatocellular carcinoma (HCC) exhibits a profoundly immunosuppressive microenvironment that limits the efficacy of current immunotherapies. This study evaluated the antitumor activity of unmodified γδ T cells in HCC and defined immune checkpoint–mediated mechanisms that restrict their therapeutic durability.
Methods
Bioinformatic analyses of LIHC datasets were performed to identify candidate prognostic T-cell receptor γ variable (TRGV) genes. Ex vivo–expanded γδ T cells were evaluated using in vitro co-culture assays with PD-L1–low (Huh7) and PD-L1–high (HCC-LM3) HCC cell lines, real-time cytotoxicity analyses, and cytokine profiling. Therapeutic efficacy, immune checkpoint regulation, and systemic safety were further assessed in subcutaneous xenograft mouse models using co-implantation and intravenous administration strategies.
Results
TRGV3 expression correlated with improved overall survival and reflected γδ T-cell presence within the tumor microenvironment. Unmodified γδ T cells exerted potent, dose-dependent cytotoxicity against HCC cells and suppressed tumor growth in vivo, particularly in PD-L1–negative models. In PD-L1–positive HCC-LM3 tumors, γδ T cell efficacy was reduced following systemic administration and was associated with tumor-induced PD-L1 upregulation, delayed cytotoxicity, and tumor recurrence. Blockade of the PD-L1/PD-1 axis restored durable γδ T cell–mediated tumor control. Importantly, γδ T-cell treatment was well tolerated, with no overt systemic toxicity observed.
Conclusion
Unmodified γδ T cells demonstrate strong antitumor activity and a favorable safety profile in HCC but are limited by adaptive PD-L1–mediated immune resistance in PD-L1–positive tumors. These findings provide a mechanistic rationale for combining γδ T cell–based therapies with immune checkpoint inhibition to enhance therapeutic efficacy in advanced HCC.
{"title":"Unmodified γδ T cells exhibit potent antitumor activity in hepatocellular carcinoma and are enhanced by PD-L1 blockade","authors":"Bo-Xiang Benjamin Zhang , Hong-Yi Lin , Hoang Yen Tran , Chung-Che Wu , Kai-Yun Chen , Tsung-I Hsu , Chih-Jie Shen","doi":"10.1016/j.imbio.2026.153163","DOIUrl":"10.1016/j.imbio.2026.153163","url":null,"abstract":"<div><h3>Objective</h3><div>Hepatocellular carcinoma (HCC) exhibits a profoundly immunosuppressive microenvironment that limits the efficacy of current immunotherapies. This study evaluated the antitumor activity of unmodified γδ T cells in HCC and defined immune checkpoint–mediated mechanisms that restrict their therapeutic durability.</div></div><div><h3>Methods</h3><div>Bioinformatic analyses of LIHC datasets were performed to identify candidate prognostic T-cell receptor γ variable (TRGV) genes. <em>Ex vivo</em>–expanded γδ T cells were evaluated using <em>in vitro</em> co-culture assays with PD-L1–low (Huh7) and PD-L1–high (HCC-LM3) HCC cell lines, real-time cytotoxicity analyses, and cytokine profiling. Therapeutic efficacy, immune checkpoint regulation, and systemic safety were further assessed in subcutaneous xenograft mouse models using co-implantation and intravenous administration strategies.</div></div><div><h3>Results</h3><div>TRGV3 expression correlated with improved overall survival and reflected γδ T-cell presence within the tumor microenvironment. Unmodified γδ T cells exerted potent, dose-dependent cytotoxicity against HCC cells and suppressed tumor growth <em>in vivo</em>, particularly in PD-L1–negative models. In PD-L1–positive HCC-LM3 tumors, γδ T cell efficacy was reduced following systemic administration and was associated with tumor-induced PD-L1 upregulation, delayed cytotoxicity, and tumor recurrence. Blockade of the PD-L1/PD-1 axis restored durable γδ T cell–mediated tumor control. Importantly, γδ T-cell treatment was well tolerated, with no overt systemic toxicity observed.</div></div><div><h3>Conclusion</h3><div>Unmodified γδ T cells demonstrate strong antitumor activity and a favorable safety profile in HCC but are limited by adaptive PD-L1–mediated immune resistance in PD-L1–positive tumors. These findings provide a mechanistic rationale for combining γδ T cell–based therapies with immune checkpoint inhibition to enhance therapeutic efficacy in advanced HCC.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 2","pages":"Article 153163"},"PeriodicalIF":2.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-18DOI: 10.1016/j.imbio.2026.153169
Luciane de Freitas Firmino , Victor Vaitkevicius-Antão , Amanda Vasconcelos Nascimento , Cíntia Nascimento Costa-Oliveira , Michelle da Silva Barros , Diego José Lira Torres , Claudeir Dias Silva-Junior , Byannca de Carvalho Torreão , Maria Beatriz Araújo Silva , Carolina de Araújo de Medeiros , Tayne Fernanda Lemos da Silva , Maria Aucineide Basílio Albuquerque , Milena Maria de Morais Silva , Filipe Prohaska Batista , Demetrius Montenegro , Wilson de Oliveira-Júnior , Cristina Carrazzone , Silvia Marinho Martins , Ana Karine Araújo Soares , Virginia Maria Barros de Lorena
The state of Pernambuco, Brazil, reported its biggest outbreak of Acute Chagas disease (ACD) caused by oral transmission, in 2019. During the acute phase, timely access to treatment must be quick and performed in all cases, regardless of the transmission route, as approximately 70–80% of cases are cured. Monitoring the immunological profile after Benznidazole (BZ) treatment in ACD patients may help identify tools to support disease progression assessment. This study aimed to evaluate the immune response, especially cytokines and antibodies levels, in patients with ACD and treated with BZ. A total of 28 laboratory-confirmed patients from the outbreak were included. Th1 and Th2 cytokines were quantified in serum samples using flow cytometry, and antibody levels were assessed by indirect immunofluorescence. Our findings indicate that BZ reduced the inflammatory response, as evidenced by decreased levels of Th1-type cytokines (IFN-γ, TNF, IL-2 and IL-6). Anti-inflammatory cytokines (IL-4 and IL-10) also showed a decline following treatment. Only IgM antibody titers were reduced, with no consistent pattern observed for IgG. These results support the use of BZ in acute phase and suggest the potential use of cytokines as auxiliary biomarkers for therapeutic monitoring.
{"title":"Immunological profile of acute Chagas disease patients infected via oral transmission and treated with Benznidazole: a two-year follow-up of immune responses","authors":"Luciane de Freitas Firmino , Victor Vaitkevicius-Antão , Amanda Vasconcelos Nascimento , Cíntia Nascimento Costa-Oliveira , Michelle da Silva Barros , Diego José Lira Torres , Claudeir Dias Silva-Junior , Byannca de Carvalho Torreão , Maria Beatriz Araújo Silva , Carolina de Araújo de Medeiros , Tayne Fernanda Lemos da Silva , Maria Aucineide Basílio Albuquerque , Milena Maria de Morais Silva , Filipe Prohaska Batista , Demetrius Montenegro , Wilson de Oliveira-Júnior , Cristina Carrazzone , Silvia Marinho Martins , Ana Karine Araújo Soares , Virginia Maria Barros de Lorena","doi":"10.1016/j.imbio.2026.153169","DOIUrl":"10.1016/j.imbio.2026.153169","url":null,"abstract":"<div><div>The state of Pernambuco, Brazil, reported its biggest outbreak of Acute Chagas disease (ACD) caused by oral transmission, in 2019. During the acute phase, timely access to treatment must be quick and performed in all cases, regardless of the transmission route, as approximately 70–80% of cases are cured. Monitoring the immunological profile after Benznidazole (BZ) treatment in ACD patients may help identify tools to support disease progression assessment. This study aimed to evaluate the immune response, especially cytokines and antibodies levels, in patients with ACD and treated with BZ. A total of 28 laboratory-confirmed patients from the outbreak were included. Th1 and Th2 cytokines were quantified in serum samples using flow cytometry, and antibody levels were assessed by indirect immunofluorescence. Our findings indicate that BZ reduced the inflammatory response, as evidenced by decreased levels of Th1-type cytokines (IFN-γ, TNF, IL-2 and IL-6). Anti-inflammatory cytokines (IL-4 and IL-10) also showed a decline following treatment. Only IgM antibody titers were reduced, with no consistent pattern observed for IgG. These results support the use of BZ in acute phase and suggest the potential use of cytokines as auxiliary biomarkers for therapeutic monitoring.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 2","pages":"Article 153169"},"PeriodicalIF":2.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-21DOI: 10.1016/j.imbio.2026.153171
Jia Liu, Yehua Jin, Sihan Wang, Xinchun Zheng
Background
Dyslipidemia is highly prevalent in patients with rheumatoid arthritis (RA) and may be closely associated with systemic inflammation and disease activity. However, its clinical characteristics and predictive factors remain unclear.
Methods
We retrospectively enrolled 312 RA patients and stratified them into dyslipidemia group (n = 168) and a normolipidemia group (n = 144) based on serum lipid profiles. Correlation analyses were performed to examine associations between lipid levels and inflammatory markers. Multivariate logistic regression was used to identify independent predictors of dyslipidemia. Receiver operating characteristic (ROC) curves were applied to evaluate the predictive performance of individual and combined models.
Results
Patients with dyslipidemia had higher levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), alongside reduced high-density lipoprotein cholesterol (HDLC). The dyslipidemia group also showed higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and Disease Activity Score in 28 joints (DAS28). TC, TG, and LDL-C were positively correlated with inflammatory markers and DAS28, while HDL-C correlated negatively. Age, body mass index (BMI), female gender, smoking history, glucocorticoid use, and higher DAS28 were identified as independent risk factors for dyslipidemia. Elevated CRP and IL-6 further increased risk, whereas higher TNF-α levels were protective. Among predictive models, the combined Integrated Model achieved superior discriminative performance, outperforming any single clinical or inflammatory indicator.
Conclusion
The integrated predictive model combining clinical and inflammatory markers improves risk discrimination, providing a useful tool for early identification of dyslipidemia in RA patients.
{"title":"Clinical characteristics and risk factors of dyslipidemia in patients with rheumatoid arthritis","authors":"Jia Liu, Yehua Jin, Sihan Wang, Xinchun Zheng","doi":"10.1016/j.imbio.2026.153171","DOIUrl":"10.1016/j.imbio.2026.153171","url":null,"abstract":"<div><h3>Background</h3><div>Dyslipidemia is highly prevalent in patients with rheumatoid arthritis (RA) and may be closely associated with systemic inflammation and disease activity. However, its clinical characteristics and predictive factors remain unclear.</div></div><div><h3>Methods</h3><div>We retrospectively enrolled 312 RA patients and stratified them into dyslipidemia group (<em>n</em> = 168) and a normolipidemia group (<em>n</em> = 144) based on serum lipid profiles. Correlation analyses were performed to examine associations between lipid levels and inflammatory markers. Multivariate logistic regression was used to identify independent predictors of dyslipidemia. Receiver operating characteristic (ROC) curves were applied to evaluate the predictive performance of individual and combined models.</div></div><div><h3>Results</h3><div>Patients with dyslipidemia had higher levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), alongside reduced high-density lipoprotein cholesterol (HDL<img>C). The dyslipidemia group also showed higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and Disease Activity Score in 28 joints (DAS28). TC, TG, and LDL-C were positively correlated with inflammatory markers and DAS28, while HDL-C correlated negatively. Age, body mass index (BMI), female gender, smoking history, glucocorticoid use, and higher DAS28 were identified as independent risk factors for dyslipidemia. Elevated CRP and IL-6 further increased risk, whereas higher TNF-α levels were protective. Among predictive models, the combined Integrated Model achieved superior discriminative performance, outperforming any single clinical or inflammatory indicator.</div></div><div><h3>Conclusion</h3><div>The integrated predictive model combining clinical and inflammatory markers improves risk discrimination, providing a useful tool for early identification of dyslipidemia in RA patients.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 2","pages":"Article 153171"},"PeriodicalIF":2.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-20DOI: 10.1016/j.imbio.2026.153159
Rohulla Vaseq , Berthila Ferkamchwi , Hans Weiher , Veronika Lukacs-Kornek , Nahid Mahleqa , Marc P. Hübner , Amit Sharma , Ingo G.H. Schmidt-Wolf
Cytokine-induced killer (CIK) cells, with dual traits resembling natural killer (NK) and T cells, have shown a promising clinical efficacy against cancer in clinical application leading to licensing of CIK cells in many countries. Here, we demonstrated that CIK cells can also inhibit the growth of Plasmodium falciparum in vitro, leading to a significant reduction in parasitemia levels after 24 h. We found that CIK cells cytotoxicity against infected RBCs is mostly dependent on their secretions rather than cell to cell communication, as they are a substantial repository of lytic agents, including granzyme B, granulysin, as well as perforin. We found that these components in the recombinant form acted synergistically, with granulysin and perforin facilitating granzyme B entry into target cells, resulting in parasite death. Moreover, we observed that priming CIK cells with dendritic cells pulsed with P. falciparum lysate antigen led to diminished CIK cell cytotoxicity against pRBCs. And finally, we found that although combination of CIK cells with chloroquine cannot be synergistic, CIK cells showed a comparable efficacy to chloroquine. Artemisinin combined with effector cells exhibited a slight enhancement in cytotoxicity compared to artemisinin alone. These results propose CIK cells as a potential alternative cell therapeutic approach in the preclinical and clinical setting against malaria and potentially other infections.
{"title":"Cytokine-induced killer (CIK) cells inhibit Plasmodium falciparum parasitemia through cytolytic effector activity in vitro","authors":"Rohulla Vaseq , Berthila Ferkamchwi , Hans Weiher , Veronika Lukacs-Kornek , Nahid Mahleqa , Marc P. Hübner , Amit Sharma , Ingo G.H. Schmidt-Wolf","doi":"10.1016/j.imbio.2026.153159","DOIUrl":"10.1016/j.imbio.2026.153159","url":null,"abstract":"<div><div>Cytokine-induced killer (CIK) cells, with dual traits resembling natural killer (NK) and T cells, have shown a promising clinical efficacy against cancer in clinical application leading to licensing of CIK cells in many countries. Here, we demonstrated that CIK cells can also inhibit the growth of <em>Plasmodium falciparum</em> in vitro, leading to a significant reduction in parasitemia levels after 24 h. We found that CIK cells cytotoxicity against infected RBCs is mostly dependent on their secretions rather than cell to cell communication, as they are a substantial repository of lytic agents, including granzyme B, granulysin, as well as perforin. We found that these components in the recombinant form acted synergistically, with granulysin and perforin facilitating granzyme B entry into target cells, resulting in parasite death. Moreover, we observed that priming CIK cells with dendritic cells pulsed with <em>P. falciparum</em> lysate antigen led to diminished CIK cell cytotoxicity against pRBCs. And finally, we found that although combination of CIK cells with chloroquine cannot be synergistic, CIK cells showed a comparable efficacy to chloroquine. Artemisinin combined with effector cells exhibited a slight enhancement in cytotoxicity compared to artemisinin alone. These results propose CIK cells as a potential alternative cell therapeutic approach in the preclinical and clinical setting against malaria and potentially other infections.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 2","pages":"Article 153159"},"PeriodicalIF":2.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-15DOI: 10.1016/j.imbio.2026.153166
Marín-Jáuregui Laura Sherell , Martínez-Shio Elena Berenice , Cárdenas-Hernández Ángel Martín , Ramírez-Torres Ricardo , Trujillo-Martíneza Aron Iván , Escobedo-Uribe Carlos David , Monsiváis-Urenda Adriana Elizabeth
The activation of the innate immune system is crucial for myocardial recovery after acute myocardial infarction (AMI). Dendritic cells (DCs) and macrophages regulate inflammation and healing of the ischemic heart. This study aims to evaluate the levels of DCs and macrophages expressing CD163 and TWEAK in patients with acute ST-elevation myocardial infarction (STEMI). We decided to evaluate the frequency of CD163+ TWEAK+ DCs and macrophages in patients with STEMI within the first 72 h, as well as at 3 and 6 months after the acute event. We observed that expression of CD163 and TWEAK in myeloid DCs was higher in STEMI patients at 3-month follow-up, and this was associated with worse cardiac function. sTWEAK levels were higher in STEMI patients within 72 h after AMI and positively correlated with a better left ventricular ejection fraction (LVEF). Finally, in M2 Macrophages, rh-TWEAK administration resulted in a dose-dependent decrease in CD163 expression. mDC, pDC, as well as M1/M2 macrophages express CD163 and TWEAK. ages. Our results indicate that TWEAK and CD163 may be promoting an inflammatory milieu after AMI. Thus, an imbalance in the expression of these molecules can then lead to chronic inflammation, tissue damage, and heart failure.
{"title":"Altered CD163 and tweak expression in dendritic cells is associated with cardiac function post-acute myocardial infarction","authors":"Marín-Jáuregui Laura Sherell , Martínez-Shio Elena Berenice , Cárdenas-Hernández Ángel Martín , Ramírez-Torres Ricardo , Trujillo-Martíneza Aron Iván , Escobedo-Uribe Carlos David , Monsiváis-Urenda Adriana Elizabeth","doi":"10.1016/j.imbio.2026.153166","DOIUrl":"10.1016/j.imbio.2026.153166","url":null,"abstract":"<div><div>The activation of the innate immune system is crucial for myocardial recovery after acute myocardial infarction (AMI). Dendritic cells (DCs) and macrophages regulate inflammation and healing of the ischemic heart. This study aims to evaluate the levels of DCs and macrophages expressing CD163 and TWEAK in patients with acute ST-elevation myocardial infarction (STEMI). We decided to evaluate the frequency of CD163+ TWEAK+ DCs and macrophages in patients with STEMI within the first 72 h, as well as at 3 and 6 months after the acute event. We observed that expression of CD163 and TWEAK in myeloid DCs was higher in STEMI patients at 3-month follow-up, and this was associated with worse cardiac function. sTWEAK levels were higher in STEMI patients within 72 h after AMI and positively correlated with a better left ventricular ejection fraction (LVEF). Finally, in M2 Macrophages, rh-TWEAK administration resulted in a dose-dependent decrease in CD163 expression. mDC, pDC, as well as M1/M2 macrophages express CD163 and TWEAK. ages. Our results indicate that TWEAK and CD163 may be promoting an inflammatory milieu after AMI. Thus, an imbalance in the expression of these molecules can then lead to chronic inflammation, tissue damage, and heart failure.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 2","pages":"Article 153166"},"PeriodicalIF":2.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146219110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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