J. Pers, Hajar Bahane, C. Le Dantec, N. Foulquier, M. Alarcón-Riquelme, P. Youinou
Further observations support the role of environmental factors in autoimmune diseases via the alteration of the epigenetic machinery. In this context, ultraviolet light, smoking, chemicals, and psychological stress have been described as likely examples of this phenomenon. For this study, we took advantage of the PRECISESADS IMI project, which gathered joint data from 2500 individuals with systemic autoimmune diseases, including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), primary Sjögren’s syndrome (pSS), rheumatoid arthritis (RA), primary antiphospholipid syndrome (PAPS), and mixed connective tissue disease (MCTD), and aimed to determine such epigenetic modifications in SLE, SSc, pSS, and RA patients. Here, we performed a set of measures in several countries from the north and south of Europe. We observed that autoimmune patients from the north of Europe presented a higher hypomethylated profile associated with an increased gene expression than patients from the south. These genes were associated with interferon (IFN) pathways, immunity, and the pathways associated with cellular metabolism. Since the IFN scores were increased in this population, these patients presented a more inflammatory profile. To conclude, the geographical location of patients with autoimmune diseases has an impact on DNA methylation, RNA expression, and immunological profiles.
{"title":"Geographic Location Determines Differentially Methylated Gene Expressions in Autoimmune Diseases","authors":"J. Pers, Hajar Bahane, C. Le Dantec, N. Foulquier, M. Alarcón-Riquelme, P. Youinou","doi":"10.3390/immuno1040037","DOIUrl":"https://doi.org/10.3390/immuno1040037","url":null,"abstract":"Further observations support the role of environmental factors in autoimmune diseases via the alteration of the epigenetic machinery. In this context, ultraviolet light, smoking, chemicals, and psychological stress have been described as likely examples of this phenomenon. For this study, we took advantage of the PRECISESADS IMI project, which gathered joint data from 2500 individuals with systemic autoimmune diseases, including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), primary Sjögren’s syndrome (pSS), rheumatoid arthritis (RA), primary antiphospholipid syndrome (PAPS), and mixed connective tissue disease (MCTD), and aimed to determine such epigenetic modifications in SLE, SSc, pSS, and RA patients. Here, we performed a set of measures in several countries from the north and south of Europe. We observed that autoimmune patients from the north of Europe presented a higher hypomethylated profile associated with an increased gene expression than patients from the south. These genes were associated with interferon (IFN) pathways, immunity, and the pathways associated with cellular metabolism. Since the IFN scores were increased in this population, these patients presented a more inflammatory profile. To conclude, the geographical location of patients with autoimmune diseases has an impact on DNA methylation, RNA expression, and immunological profiles.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85308227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Constantin Ißleib, Susanne Kurz, Samuel Scholl, Bettina Amberg, J. Spohn
Human mesenchymal stem cells (hMSCs) are well-known for their immunomodulatory potential. In recent clinical trials and in vivo studies, hMSCs were used as therapeutic measures to dampen inflammation. In this context, their effect on macrophages in vivo has been described to induce a phenotype change shifting from a proinflammatory to an anti-inflammatory environment. Despite several in vitro studies that investigated the potential of hMSCs to inhibit the polarization of macrophages into the proinflammatory M1 subtype, it is still unclear if hMSCs affect polarized M1 macrophages or if they control the environment by inhibiting the M1 polarization of unpolarized macrophages. Here, a comparative in vitro investigation of hMSC immunomodulation via soluble factors concerning the influence on the polarization of macrophages to M1 and on polarized M1 macrophages is presented. Human primary monocyte-derived macrophages (hMDMs) as well as THP-1 cells were used for this investigation. The macrophage subtype was analyzed by gene expression as well as cytokine secretion. hMSCs affected cytokine secretion of polarizing macrophages, while changes in gene expression were evident in polarized M1 macrophages. These effects were observed in THP-1 and hMDM macrophages. In conclusion, we suggest that hMSCs implement their immunomodulatory effects on polarizing and polarized macrophages in different ways.
{"title":"Plasticity of Proinflammatory Macrophages Depends on Their Polarization Stage during Human MSC Immunomodulation—An In Vitro Study Using THP-1 and Human Primary Macrophages","authors":"Constantin Ißleib, Susanne Kurz, Samuel Scholl, Bettina Amberg, J. Spohn","doi":"10.3390/immuno1040036","DOIUrl":"https://doi.org/10.3390/immuno1040036","url":null,"abstract":"Human mesenchymal stem cells (hMSCs) are well-known for their immunomodulatory potential. In recent clinical trials and in vivo studies, hMSCs were used as therapeutic measures to dampen inflammation. In this context, their effect on macrophages in vivo has been described to induce a phenotype change shifting from a proinflammatory to an anti-inflammatory environment. Despite several in vitro studies that investigated the potential of hMSCs to inhibit the polarization of macrophages into the proinflammatory M1 subtype, it is still unclear if hMSCs affect polarized M1 macrophages or if they control the environment by inhibiting the M1 polarization of unpolarized macrophages. Here, a comparative in vitro investigation of hMSC immunomodulation via soluble factors concerning the influence on the polarization of macrophages to M1 and on polarized M1 macrophages is presented. Human primary monocyte-derived macrophages (hMDMs) as well as THP-1 cells were used for this investigation. The macrophage subtype was analyzed by gene expression as well as cytokine secretion. hMSCs affected cytokine secretion of polarizing macrophages, while changes in gene expression were evident in polarized M1 macrophages. These effects were observed in THP-1 and hMDM macrophages. In conclusion, we suggest that hMSCs implement their immunomodulatory effects on polarizing and polarized macrophages in different ways.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82173044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. Southey, Marissa R. Keever-Keigher, Haley E. Rymut, L. Rund, Rodney W. Johnson, S. Rodriguez-Zas
The inflammatory response of gestating females to infection or stress can disrupt gene expression in the offspring’s amygdala, resulting in lasting neurodevelopmental, physiological, and behavioral disorders. The effects of maternal immune activation (MIA) can be impacted by the offspring’s sex and exposure to additional stressors later in life. The objectives of this study were to investigate the disruption of alternative splicing patterns associated with MIA in the offspring’s amygdala and characterize this disruption in the context of the second stress of weaning and sex. Differential alternative splicing was tested on the RNA-seq profiles of a pig model of viral-induced MIA. Compared to controls, MIA was associated with the differential alternative splicing (FDR-adjusted p-value < 0.1) of 292 and 240 genes in weaned females and males, respectively, whereas 132 and 176 genes were differentially spliced in control nursed female and male, respectively. The majority of the differentially spliced (FDR-adjusted p-value < 0.001) genes (e.g., SHANK1, ZNF672, KCNA6) and many associated enriched pathways (e.g., Fc gamma R-mediated phagocytosis, non-alcoholic fatty liver disease, and cGMP-PKG signaling) have been reported in MIA-related disorders including autism and schizophrenia in humans. Differential alternative splicing associated with MIA was detected in the gene MAG across all sex-stress groups except for unstressed males and SLC2A11 across all groups except unstressed females. Precise understanding of the effect of MIA across second stressors and sexes necessitates the consideration of splicing isoform profiles.
{"title":"Disruption of Alternative Splicing in the Amygdala of Pigs Exposed to Maternal Immune Activation","authors":"B. Southey, Marissa R. Keever-Keigher, Haley E. Rymut, L. Rund, Rodney W. Johnson, S. Rodriguez-Zas","doi":"10.3390/immuno1040035","DOIUrl":"https://doi.org/10.3390/immuno1040035","url":null,"abstract":"The inflammatory response of gestating females to infection or stress can disrupt gene expression in the offspring’s amygdala, resulting in lasting neurodevelopmental, physiological, and behavioral disorders. The effects of maternal immune activation (MIA) can be impacted by the offspring’s sex and exposure to additional stressors later in life. The objectives of this study were to investigate the disruption of alternative splicing patterns associated with MIA in the offspring’s amygdala and characterize this disruption in the context of the second stress of weaning and sex. Differential alternative splicing was tested on the RNA-seq profiles of a pig model of viral-induced MIA. Compared to controls, MIA was associated with the differential alternative splicing (FDR-adjusted p-value < 0.1) of 292 and 240 genes in weaned females and males, respectively, whereas 132 and 176 genes were differentially spliced in control nursed female and male, respectively. The majority of the differentially spliced (FDR-adjusted p-value < 0.001) genes (e.g., SHANK1, ZNF672, KCNA6) and many associated enriched pathways (e.g., Fc gamma R-mediated phagocytosis, non-alcoholic fatty liver disease, and cGMP-PKG signaling) have been reported in MIA-related disorders including autism and schizophrenia in humans. Differential alternative splicing associated with MIA was detected in the gene MAG across all sex-stress groups except for unstressed males and SLC2A11 across all groups except unstressed females. Precise understanding of the effect of MIA across second stressors and sexes necessitates the consideration of splicing isoform profiles.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84438817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Reyes-Castillo, R. González-Vázquez, E. Torres-Maravilla, M. Tello, L. Bermúdez-Humarán, L. Mayorga-Reyes
Viral infections represent a major health problem worldwide. Due to the wide variety of etiological agents and their increasing resistance to anti-virals and antibiotics treatments, new strategies for effective therapies need to be developed. Scientific evidence suggests that probiotics may have prophylactic and therapeutic effects in viral diseases. Indeed, these microorganisms interact harmoniously with the intestinal microbiota and protect the integrity of the intestinal barrier as well as modulate the host immune system. Currently, clinical trials with probiotics have been documented in respiratory tract infections, infections caused by human immunodeficiency viruses, herpes, human papillomavirus and hepatic encephalopathy. However, the benefits documented so far are difficult to extrapolate, due to the strain-dependent effect. In addition, the dose of the microorganism used as well as host characteristics are other parameters that should be consider when advocating the use of probiotics to treat viral infections. This review addresses the scientific evidence of the efficacy of probiotics in clinical strains perspective in viral infectious diseases in the last 10 years.
{"title":"Probiotics against Viral Infections: Current Clinical Trials and Future Perspectives","authors":"P. Reyes-Castillo, R. González-Vázquez, E. Torres-Maravilla, M. Tello, L. Bermúdez-Humarán, L. Mayorga-Reyes","doi":"10.3390/immuno1040034","DOIUrl":"https://doi.org/10.3390/immuno1040034","url":null,"abstract":"Viral infections represent a major health problem worldwide. Due to the wide variety of etiological agents and their increasing resistance to anti-virals and antibiotics treatments, new strategies for effective therapies need to be developed. Scientific evidence suggests that probiotics may have prophylactic and therapeutic effects in viral diseases. Indeed, these microorganisms interact harmoniously with the intestinal microbiota and protect the integrity of the intestinal barrier as well as modulate the host immune system. Currently, clinical trials with probiotics have been documented in respiratory tract infections, infections caused by human immunodeficiency viruses, herpes, human papillomavirus and hepatic encephalopathy. However, the benefits documented so far are difficult to extrapolate, due to the strain-dependent effect. In addition, the dose of the microorganism used as well as host characteristics are other parameters that should be consider when advocating the use of probiotics to treat viral infections. This review addresses the scientific evidence of the efficacy of probiotics in clinical strains perspective in viral infectious diseases in the last 10 years.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73658223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Labanca, V. Cacciato, P. Borro, S. Marenco, G. Pieri, A. Picciotto, M. C. Plaz Torres, E. Giannini
Obeticholic acid (OCA) improves cholestasis and is generally well tolerated in patients with primary biliary cholangitis (PBC) not responding, or intolerant, to ursodeoxycholic acid (UDCA). As PBC is mainly a cholestatic disorder, less attention is paid to aminotransferase behavior in the course of treatment. In this study we evaluated, in clinical practice, the efficacy of OCA treatment on both alkaline phosphatase (ALP) and alanine aminotransferase (ALT) using updated healthy ranges for aminotransferases. Fifteen PBC patients, non-responders to UDCA, were evaluated at baseline and during OCA treatment with serial measurement of cholestasis indexes and ALT, that were also assessed using updated normal ranges (<30 IU/L in males, <19 IU/L in females). Median ALP and ALT decreased from 2.16 to 1.27 × upper limit of normal (p = 0.003) and from 0.93 to 0.78 × upper limit of normal (p = 0.008), respectively, in the course of OCA treatment. At treatment day-15, median ALT decreased by 29.7% and ALP by 8.8%. Bilirubin and albumin were unmodified throughout treatment. Using updated normal ranges, ALT levels were normal in 6.7% of patients at baseline and in 33.3% of patients at 18 months of treatment. OCA treatment improves cholestasis and, also, indexes of hepatocyte necrosis, with a decline in necro-inflammatory activity even predating the improvement in cholestasis. Use of recalibrated healthy ranges for aminotransferases might be a useful tool to assess hepatic histological activity and its improvement with OCA treatment.
{"title":"Obeticholic Acid Improves Aminotransferases Early during Treatment in Patients with Primary Biliary Cholangitis Not Responding to Ursodeoxycholic Acid: A Study in Clinical Practice","authors":"S. Labanca, V. Cacciato, P. Borro, S. Marenco, G. Pieri, A. Picciotto, M. C. Plaz Torres, E. Giannini","doi":"10.3390/immuno1040033","DOIUrl":"https://doi.org/10.3390/immuno1040033","url":null,"abstract":"Obeticholic acid (OCA) improves cholestasis and is generally well tolerated in patients with primary biliary cholangitis (PBC) not responding, or intolerant, to ursodeoxycholic acid (UDCA). As PBC is mainly a cholestatic disorder, less attention is paid to aminotransferase behavior in the course of treatment. In this study we evaluated, in clinical practice, the efficacy of OCA treatment on both alkaline phosphatase (ALP) and alanine aminotransferase (ALT) using updated healthy ranges for aminotransferases. Fifteen PBC patients, non-responders to UDCA, were evaluated at baseline and during OCA treatment with serial measurement of cholestasis indexes and ALT, that were also assessed using updated normal ranges (<30 IU/L in males, <19 IU/L in females). Median ALP and ALT decreased from 2.16 to 1.27 × upper limit of normal (p = 0.003) and from 0.93 to 0.78 × upper limit of normal (p = 0.008), respectively, in the course of OCA treatment. At treatment day-15, median ALT decreased by 29.7% and ALP by 8.8%. Bilirubin and albumin were unmodified throughout treatment. Using updated normal ranges, ALT levels were normal in 6.7% of patients at baseline and in 33.3% of patients at 18 months of treatment. OCA treatment improves cholestasis and, also, indexes of hepatocyte necrosis, with a decline in necro-inflammatory activity even predating the improvement in cholestasis. Use of recalibrated healthy ranges for aminotransferases might be a useful tool to assess hepatic histological activity and its improvement with OCA treatment.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88379380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keshav Goyal, Harsh Goel, Pritika Baranwal, Anisha Tewary, Aman Dixit, A. Pandey, Mercilena Benjamin, P. Tanwar, A. Dey, Fahad Khan, P. Pandey, P. Gupta, Dhruv Kumar, S. Roychoudhury, N. Jha, T. Upadhyay, K. Kesari
The SARS-CoV-2 infection spread rapidly throughout the world and appears to involve in both humoral and cell-mediated immunity. SARS-CoV-2 is attached to host cells via binding to the viral spike (S) proteins and its cellular receptors angiotensin-converting enzyme 2 (ACE2). Consequently, the S protein is primed with serine proteases TMPRSS2 and TMPRSS4, which facilitate the fusion of viral and cellular membranes result in the entry of viral RNA into the host cell. Vaccines are urgently required to combat the coronavirus disease 2019 (COVID-19) outbreak and aid in the recovery to pre-pandemic levels of normality. The long-term protective immunity is provided by the vaccine antigen (or pathogen)-specific immune effectors and the activation of immune memory cells that can be efficiently and rapidly reactivated upon pathogen exposure. Research efforts aimed towards the design and development of vaccines for SARS-CoV-2 are increasing. Numerous coronavirus disease 2019 (COVID-19) vaccines have passed late-stage clinical investigations with promising outcomes. This review focuses on the present state and future prospects of COVID-19 vaccines research and development, with a particular emphasis on immunological mechanisms of various COVID-19vaccines such as adenoviral vector-based vaccines, mRNA vaccines, and DNA vaccines that elicits immunological responses against SARS-CoV-2 infections in humans.
{"title":"Immunological Mechanisms of Vaccine-Induced Protection against SARS-CoV-2 in Humans","authors":"Keshav Goyal, Harsh Goel, Pritika Baranwal, Anisha Tewary, Aman Dixit, A. Pandey, Mercilena Benjamin, P. Tanwar, A. Dey, Fahad Khan, P. Pandey, P. Gupta, Dhruv Kumar, S. Roychoudhury, N. Jha, T. Upadhyay, K. Kesari","doi":"10.3390/immuno1040032","DOIUrl":"https://doi.org/10.3390/immuno1040032","url":null,"abstract":"The SARS-CoV-2 infection spread rapidly throughout the world and appears to involve in both humoral and cell-mediated immunity. SARS-CoV-2 is attached to host cells via binding to the viral spike (S) proteins and its cellular receptors angiotensin-converting enzyme 2 (ACE2). Consequently, the S protein is primed with serine proteases TMPRSS2 and TMPRSS4, which facilitate the fusion of viral and cellular membranes result in the entry of viral RNA into the host cell. Vaccines are urgently required to combat the coronavirus disease 2019 (COVID-19) outbreak and aid in the recovery to pre-pandemic levels of normality. The long-term protective immunity is provided by the vaccine antigen (or pathogen)-specific immune effectors and the activation of immune memory cells that can be efficiently and rapidly reactivated upon pathogen exposure. Research efforts aimed towards the design and development of vaccines for SARS-CoV-2 are increasing. Numerous coronavirus disease 2019 (COVID-19) vaccines have passed late-stage clinical investigations with promising outcomes. This review focuses on the present state and future prospects of COVID-19 vaccines research and development, with a particular emphasis on immunological mechanisms of various COVID-19vaccines such as adenoviral vector-based vaccines, mRNA vaccines, and DNA vaccines that elicits immunological responses against SARS-CoV-2 infections in humans.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76358821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To develop efficient applications of monoclonal antibodies for therapeutic purposes, stereospecific recognition of the target antigens is needed. DNA immunization is one of the best methods for sensitizing B lymphocytes that can produce conformation-specific antibodies. Here we verified the class-switching of monoclonal antibodies by DNA immunization followed by cell immunization for the generation of stereospecific monoclonal antibodies against native G protein-coupled receptor (GPCR) using the optimized stereospecific targeting (SST) technique. This technology facilitates the efficient selection of sensitized B lymphocytes through specific interaction with the intact antigen via B-cell receptors (BCRs). We demonstrate that multiple DNA immunizations followed by a single cell immunization in combination with a longer sensitization period (three to four months) are an appropriate sensitizing strategy for the generation of IgG-type stereospecific monoclonal antibodies by class-switching, and the characteristics of antibody production could be transferred to hybridoma cells provided by the optimized SST technique.
{"title":"Class-Switching of B Lymphocytes by DNA and Cell Immunization for Stereospecific Monoclonal Antibodies against Native GPCR","authors":"Yushi Isozaki, K. Tsumoto, M. Tomita","doi":"10.3390/immuno1040031","DOIUrl":"https://doi.org/10.3390/immuno1040031","url":null,"abstract":"To develop efficient applications of monoclonal antibodies for therapeutic purposes, stereospecific recognition of the target antigens is needed. DNA immunization is one of the best methods for sensitizing B lymphocytes that can produce conformation-specific antibodies. Here we verified the class-switching of monoclonal antibodies by DNA immunization followed by cell immunization for the generation of stereospecific monoclonal antibodies against native G protein-coupled receptor (GPCR) using the optimized stereospecific targeting (SST) technique. This technology facilitates the efficient selection of sensitized B lymphocytes through specific interaction with the intact antigen via B-cell receptors (BCRs). We demonstrate that multiple DNA immunizations followed by a single cell immunization in combination with a longer sensitization period (three to four months) are an appropriate sensitizing strategy for the generation of IgG-type stereospecific monoclonal antibodies by class-switching, and the characteristics of antibody production could be transferred to hybridoma cells provided by the optimized SST technique.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"204 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77747800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MHC class I molecules display intracellular peptides on cell surfaces to enable immune surveillance under pathological conditions. The source of MHC class I antigens responsible for cancer protection is not fully understood. Here, we explored the MHC class I peptidome in mouse colon cancer cells using a proteogenomic approach. We showed that cryptic peptides derived from unconventional short open reading frames accounted for part of the MHC class I peptidome. Moreover, cancer growth was significantly prevented in mice immunized with a cocktail of synthesized cryptic peptides. Together, our data showed that the source of cancer antigens was not limited to fragments of consensus proteins. Cryptic antigens were displayed by MHC molecules and mediated anti-cancer effects, suggesting their therapeutic potential for cancer prevention.
{"title":"Therapeutic Potential of Cancer Vaccine Based on MHC Class I Cryptic Peptides Derived from Non-Coding Regions","authors":"S. Tokita, T. Kanaseki, T. Torigoe","doi":"10.3390/immuno1040030","DOIUrl":"https://doi.org/10.3390/immuno1040030","url":null,"abstract":"MHC class I molecules display intracellular peptides on cell surfaces to enable immune surveillance under pathological conditions. The source of MHC class I antigens responsible for cancer protection is not fully understood. Here, we explored the MHC class I peptidome in mouse colon cancer cells using a proteogenomic approach. We showed that cryptic peptides derived from unconventional short open reading frames accounted for part of the MHC class I peptidome. Moreover, cancer growth was significantly prevented in mice immunized with a cocktail of synthesized cryptic peptides. Together, our data showed that the source of cancer antigens was not limited to fragments of consensus proteins. Cryptic antigens were displayed by MHC molecules and mediated anti-cancer effects, suggesting their therapeutic potential for cancer prevention.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80729915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. De Felice, Mariagrazia Tammaro, D. Leopardo, G. Ianniello, G. Turitto
The abscopal effect (AbE) is defined as radiation-induced shrinkage of distant, non-treated, neoplastic lesions and it is considered the best clinical picture of the efficient immune stimulation by irradiation. The first report about abscopal tumor regression upon radiotherapy dates back to the beginning of the 20th century. The growing preclinical and clinical synergism between radiation and immunotherapy gave birth the purpose to more easily reproduce the abscopal effect, nevertheless, it is still rare in clinical practice. In this review we summarize immunological modulation of radiotherapy, focusing on the well-balanced equilibrium of tumor microenvironment and how radio-immunotherapy combinations can perturb it, with particular attention on head and neck squamous cell cancer. Finally, we investigate future perspectives, with the aim to “tailor” the abscopal effect to the patient.
{"title":"Moving towards the Future of Radio-Immunotherapy: Could We “Tailor” the Abscopal Effect on Head and Neck Cancer Patients?","authors":"M. De Felice, Mariagrazia Tammaro, D. Leopardo, G. Ianniello, G. Turitto","doi":"10.3390/immuno1040029","DOIUrl":"https://doi.org/10.3390/immuno1040029","url":null,"abstract":"The abscopal effect (AbE) is defined as radiation-induced shrinkage of distant, non-treated, neoplastic lesions and it is considered the best clinical picture of the efficient immune stimulation by irradiation. The first report about abscopal tumor regression upon radiotherapy dates back to the beginning of the 20th century. The growing preclinical and clinical synergism between radiation and immunotherapy gave birth the purpose to more easily reproduce the abscopal effect, nevertheless, it is still rare in clinical practice. In this review we summarize immunological modulation of radiotherapy, focusing on the well-balanced equilibrium of tumor microenvironment and how radio-immunotherapy combinations can perturb it, with particular attention on head and neck squamous cell cancer. Finally, we investigate future perspectives, with the aim to “tailor” the abscopal effect to the patient.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74082520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Mensah, A. N. Boakye, Anthony Basingnaa, E. Owusu, S. Antwi-Baffour, M. Ofori, K. Addo, D. Jackson-Sillah, T. Adékambi
Existing tools (including GeneXpert) for diagnosis of multidrug resistant TB (MDR-TB) have limited utility when sputum samples for microbiological analyses cannot be obtained. There is the need for immunological biomarkers which could serve as putative diagnostic markers of MDR-TB. We measured and compared the serum cytokine levels of inflammatory cytokines (IFN-γ, TNF-α, IL12p70, IL-17A, granzyme B) and anti-inflammatory cytokines (IL-10, IL-6, IL-4) among MDR-TB, drug-susceptible (DS)-TB and healthy controls (no-TB) using the Human Magnetic Luminex Multiplex Immunoassay. Levels of IFN-γ and IL-4 were respectively 1.5 log lower and 1.9 log higher in MDR-TB compared to DS-TB cases. Moreover, IFN-γ, TNF-α, IL-10, IL-6, and IL-4 levels were significantly higher in individuals with MDR-TB and DS-TB cases compared to healthy controls. Pairs of cytokines, IL-4 and IFN-γ (p = 0.019), IL-4 and TNF (p = 0.019), and Granzyme B and TNF-α (p = 0.019), showed significant positive correlation in MDR-TB. Serum cytokine profiles can be exploited for immunodiagnostics, as made evident by the Interferon Gamma Release Assays (IGRAs) for TB infection. Using area under the curve values, no single or multiple cytokine combinations could discriminate between DS- and MDR-TB in this study. Studies with a larger sample size and more cytokines could better address the issue.
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