Pub Date : 2023-12-20DOI: 10.1038/s41435-023-00232-9
Kubra Uslu, Firat Ozcelik, Gokmen Zararsiz, Vahap Eldem, Ahu Cephe, Izem Olcay Sahin, Recep Civan Yuksel, Hilal Sipahioglu, Zuhal Ozer Simsek, Osman Baspinar, Hilal Akalin, Yasin Simsek, Kursat Gundogan, Nuri Tutar, Aynur Karayol Akin, Yusuf Ozkul, Orhan Yildiz, Munis Dundar
The COVID-19 pandemic remains a significant public health concern despite the new vaccines and therapeutics. The clinical course of acute SARS-CoV-2 infection is highly variable and influenced by several factors related to the virus and the host. Numerous genetic studies, including candidate gene, exome, and genome sequencing studies, genome-wide association studies, and other omics efforts, have proposed various Mendelian and non-Mendelian associations with COVID-19 course. In this study, we conducted whole-exome sequencing on 90 unvaccinated patients from Turkey with no known comorbidities associated with severe COVID-19. Of these patients, 30 had severe, 30 had moderate, and 30 had mild/asymptomatic disease. We identified rare variants in genes associated with SARS-CoV-2 susceptibility and pathogenesis, with an emphasis on genes related to the regulation of inflammation, and discussed these in the context of the clinical course of the patients. In addition, we compared the frequencies of common variants between each group. Even though no variant remained statistically significant after correction for multiple testing, we observed that certain previously associated genes and variants showed significant associations before correction. Our study contributes to the existing literature regarding the genetic susceptibility to SARS-CoV-2. Future studies would be beneficial characterizing the host genetic properties in different populations.
{"title":"Deciphering the host genetic factors conferring susceptibility to severe COVID-19 using exome sequencing","authors":"Kubra Uslu, Firat Ozcelik, Gokmen Zararsiz, Vahap Eldem, Ahu Cephe, Izem Olcay Sahin, Recep Civan Yuksel, Hilal Sipahioglu, Zuhal Ozer Simsek, Osman Baspinar, Hilal Akalin, Yasin Simsek, Kursat Gundogan, Nuri Tutar, Aynur Karayol Akin, Yusuf Ozkul, Orhan Yildiz, Munis Dundar","doi":"10.1038/s41435-023-00232-9","DOIUrl":"10.1038/s41435-023-00232-9","url":null,"abstract":"The COVID-19 pandemic remains a significant public health concern despite the new vaccines and therapeutics. The clinical course of acute SARS-CoV-2 infection is highly variable and influenced by several factors related to the virus and the host. Numerous genetic studies, including candidate gene, exome, and genome sequencing studies, genome-wide association studies, and other omics efforts, have proposed various Mendelian and non-Mendelian associations with COVID-19 course. In this study, we conducted whole-exome sequencing on 90 unvaccinated patients from Turkey with no known comorbidities associated with severe COVID-19. Of these patients, 30 had severe, 30 had moderate, and 30 had mild/asymptomatic disease. We identified rare variants in genes associated with SARS-CoV-2 susceptibility and pathogenesis, with an emphasis on genes related to the regulation of inflammation, and discussed these in the context of the clinical course of the patients. In addition, we compared the frequencies of common variants between each group. Even though no variant remained statistically significant after correction for multiple testing, we observed that certain previously associated genes and variants showed significant associations before correction. Our study contributes to the existing literature regarding the genetic susceptibility to SARS-CoV-2. Future studies would be beneficial characterizing the host genetic properties in different populations.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 1","pages":"14-42"},"PeriodicalIF":5.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138821636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-19DOI: 10.1038/s41435-023-00219-6
Thomas R. Müller, Marcus Buggert
{"title":"Boosting SARS-CoV-2 immunity in immunocompromised individuals","authors":"Thomas R. Müller, Marcus Buggert","doi":"10.1038/s41435-023-00219-6","DOIUrl":"10.1038/s41435-023-00219-6","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 2","pages":"168-169"},"PeriodicalIF":5.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-023-00219-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-16DOI: 10.1038/s41435-023-00235-6
Jingjing Zhu, Benoit J. Van den Eynde
{"title":"AHR and tryptophan metabolism: a collaborative dynamics of immune regulation","authors":"Jingjing Zhu, Benoit J. Van den Eynde","doi":"10.1038/s41435-023-00235-6","DOIUrl":"10.1038/s41435-023-00235-6","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 2","pages":"170-171"},"PeriodicalIF":5.0,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138682066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-15DOI: 10.1038/s41435-023-00237-4
Olga Zimmermannova, Alexandra Gabriela Ferreira, Carlos-Filipe Pereira
{"title":"Orchestrating an immune response to cancer with cellular reprogramming","authors":"Olga Zimmermannova, Alexandra Gabriela Ferreira, Carlos-Filipe Pereira","doi":"10.1038/s41435-023-00237-4","DOIUrl":"10.1038/s41435-023-00237-4","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 1","pages":"95-97"},"PeriodicalIF":5.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-023-00237-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138681985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-14DOI: 10.1038/s41435-023-00236-5
Feifei Wei, Tetsuro Sasada
{"title":"Circulating cytokine signatures as a soluble biomarker of immune checkpoint inhibitor therapy in non-small-cell lung cancer","authors":"Feifei Wei, Tetsuro Sasada","doi":"10.1038/s41435-023-00236-5","DOIUrl":"10.1038/s41435-023-00236-5","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 1","pages":"89-91"},"PeriodicalIF":5.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138630396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-14DOI: 10.1038/s41435-023-00238-3
Corey T. Watson, Oscar L. Rodriguez, Eric Engelbrecht, Yana Safonova, Wayne A. Marasco, Melissa L. Smith
{"title":"Looking to the future of antibody genetics: resolving the roles of immunoglobulin diversity in gene regulation, function, and immunity","authors":"Corey T. Watson, Oscar L. Rodriguez, Eric Engelbrecht, Yana Safonova, Wayne A. Marasco, Melissa L. Smith","doi":"10.1038/s41435-023-00238-3","DOIUrl":"10.1038/s41435-023-00238-3","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 1","pages":"92-94"},"PeriodicalIF":5.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138630493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-13DOI: 10.1038/s41435-023-00240-9
John G. Lenehan, Saman Maleki Vareki
{"title":"An adjunct microbiome therapy to enhance immunotherapy efficacy in melanoma patients","authors":"John G. Lenehan, Saman Maleki Vareki","doi":"10.1038/s41435-023-00240-9","DOIUrl":"10.1038/s41435-023-00240-9","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 1","pages":"87-88"},"PeriodicalIF":5.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138630477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-13DOI: 10.1038/s41435-023-00239-2
Subir Biswas, Carmen M. Anadon, Jose R. Conejo-Garcia
{"title":"Antibodies target intracellular oncodrivers through PIGR-mediated transcytosis","authors":"Subir Biswas, Carmen M. Anadon, Jose R. Conejo-Garcia","doi":"10.1038/s41435-023-00239-2","DOIUrl":"10.1038/s41435-023-00239-2","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 1","pages":"85-86"},"PeriodicalIF":5.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138580988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-13DOI: 10.1038/s41435-023-00234-7
Xiaopeng Zhao, Chuang Liu, Licheng Peng, Hongyan Wang
Metformin is a synthetic biguanide proven to have beneficial effects against various human diseases. Research has confirmed that metformin exerts its effects by regulating the composition of intestinal microbiota. The composition of intestinal microbiota influences the efficacy of anti-PD-L1 immunotherapy. We assume that the regulation of metformin on intestinal microbiota could enhance the therapeutic efficiency of anti-PD-L1 antibodies. In Lewis lung cancer-bearing C57BL/6J mice, we find that metformin enhances PD-L1 antibody efficacy mainly depending on the existence of gut microbiota, and metformin increases the anti-tumor immunity through modulation of intestinal microbiota and affects the integrity of the intestinal mucosa. Antibiotic depletion of gut microbiota abolished the combination efficacy of PD-L1 antibody and metformin, implying the significance of intestinal microbiota in metformin’s antitumor action. Combining anti-PD-L1 antibody with metformin provoked tumor necrosis by causing increased CD8 T-cell infiltration and IFN-γ expression. In conclusion, metformin could be employed as a microecological controller to prompt antitumor immunity and increase the efficacy of anti-PD-L1 antibodies. Our study provided reliable evidence that metformin could be synergistically used with anti-PD-L1 antibody to enhance the anti-cancer effect.
{"title":"Metformin facilitates anti-PD-L1 efficacy through the regulation of intestinal microbiota","authors":"Xiaopeng Zhao, Chuang Liu, Licheng Peng, Hongyan Wang","doi":"10.1038/s41435-023-00234-7","DOIUrl":"10.1038/s41435-023-00234-7","url":null,"abstract":"Metformin is a synthetic biguanide proven to have beneficial effects against various human diseases. Research has confirmed that metformin exerts its effects by regulating the composition of intestinal microbiota. The composition of intestinal microbiota influences the efficacy of anti-PD-L1 immunotherapy. We assume that the regulation of metformin on intestinal microbiota could enhance the therapeutic efficiency of anti-PD-L1 antibodies. In Lewis lung cancer-bearing C57BL/6J mice, we find that metformin enhances PD-L1 antibody efficacy mainly depending on the existence of gut microbiota, and metformin increases the anti-tumor immunity through modulation of intestinal microbiota and affects the integrity of the intestinal mucosa. Antibiotic depletion of gut microbiota abolished the combination efficacy of PD-L1 antibody and metformin, implying the significance of intestinal microbiota in metformin’s antitumor action. Combining anti-PD-L1 antibody with metformin provoked tumor necrosis by causing increased CD8 T-cell infiltration and IFN-γ expression. In conclusion, metformin could be employed as a microecological controller to prompt antitumor immunity and increase the efficacy of anti-PD-L1 antibodies. Our study provided reliable evidence that metformin could be synergistically used with anti-PD-L1 antibody to enhance the anti-cancer effect.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 1","pages":"7-13"},"PeriodicalIF":5.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138630471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-11DOI: 10.1038/s41435-023-00224-9
Johannes C. Melms, Patricia Ho, Meri Rogava, Benjamin Izar
Immune evasion is a hallmark of cancer, yet the underlying mechanisms are often unknown in many patients. Using single-cell transcriptomics analysis, we previously identified the co-stimulator CD58 as part of a cancer cell-intrinsic immune checkpoint resistance signature in patient melanoma tissue. We subsequently validated CD58 loss as a driver of immune evasion using a patient-derived co-culture model of cancer and cytotoxic tumor-infiltrating lymphocytes in a pooled single-cell perturbation experiment, where we additionally observed concurrent upregulation of PD-L1 protein expression in melanoma cells with CD58 loss. In our most recent study, we uncovered the mechanisms of immune evasion mediated by CD58 loss, including impaired T cell activation and infiltration within tumors, as well as inhibitory signaling by PD-L1 via a shared regulator, CMTM6. Thus, cancer cell-intrinsic reduction of CD58 represents a multi-faceted determinant of immune evasion. Furthermore, its reciprocal interaction with PD-L1 via CMTM6 provides critical insights into how co-inhibitory and co-stimulatory immune cues are regulated.
{"title":"From patient tissue correlates to molecular mechanisms of cancer immune evasion: the emerging role of CD58 and PD-L1 co-regulation via CMTM6","authors":"Johannes C. Melms, Patricia Ho, Meri Rogava, Benjamin Izar","doi":"10.1038/s41435-023-00224-9","DOIUrl":"10.1038/s41435-023-00224-9","url":null,"abstract":"Immune evasion is a hallmark of cancer, yet the underlying mechanisms are often unknown in many patients. Using single-cell transcriptomics analysis, we previously identified the co-stimulator CD58 as part of a cancer cell-intrinsic immune checkpoint resistance signature in patient melanoma tissue. We subsequently validated CD58 loss as a driver of immune evasion using a patient-derived co-culture model of cancer and cytotoxic tumor-infiltrating lymphocytes in a pooled single-cell perturbation experiment, where we additionally observed concurrent upregulation of PD-L1 protein expression in melanoma cells with CD58 loss. In our most recent study, we uncovered the mechanisms of immune evasion mediated by CD58 loss, including impaired T cell activation and infiltration within tumors, as well as inhibitory signaling by PD-L1 via a shared regulator, CMTM6. Thus, cancer cell-intrinsic reduction of CD58 represents a multi-faceted determinant of immune evasion. Furthermore, its reciprocal interaction with PD-L1 via CMTM6 provides critical insights into how co-inhibitory and co-stimulatory immune cues are regulated.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 1","pages":"82-84"},"PeriodicalIF":5.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138574751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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