Major Histocompatibility Complex Genes as Therapeutic Opportunity for Immune Cold Molecular Cancer Subtypes
Current immunotherapies are effective only in a subset of patients, likely due to several factors including defects in tumor cell antigen presentation, decreased response to immune effectors, and molecular heterogeneity of cancers. Recent molecular classifications enable the categorization of many t...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2020/8758090 |
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| author | Paweł Karpiński Łukasz Łaczmański Maria M. Sąsiadek |
| author_facet | Paweł Karpiński Łukasz Łaczmański Maria M. Sąsiadek |
| author_sort | Paweł Karpiński |
| collection | DOAJ |
| description | Current immunotherapies are effective only in a subset of patients, likely due to several factors including defects in tumor cell antigen presentation, decreased response to immune effectors, and molecular heterogeneity of cancers. Recent molecular classifications enable the categorization of many tumor types. However, deregulation of major histocompatibility complex (MHC) gene expression is poorly characterized in the context of molecular cancer subtypes. To suppress the confounding effect of immune infiltrates on expression patterns of immunoregulators, we identified and removed genes with strong correlation to estimated immune compartment levels in each tumor type. Next, we reanalyzed a total of 13 TCGA cancer types encompassing 5651 tumors and 485 normal adjacent tissues by performing unsupervised clustering of 14 MHC genes. Subsequently, resultant clusters were statistically compared in terms of expression of other immune-related genes. Three MHC expression clusters were discovered by unsupervised clustering. We identified concordantly decreased expression of MHC genes (MHC-low) in 26 out of 55 molecular subtypes. Consequently, our study underlines the urgent need for designing strategies to enhance tumor MHC expression that could improve immune cold tumor rejection by cytotoxic T lymphocytes. |
| format | Article |
| id | doaj-art-b50e0f78ea0f4f0581532d981b5f6f26 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-b50e0f78ea0f4f0581532d981b5f6f262025-02-03T06:43:30ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/87580908758090Major Histocompatibility Complex Genes as Therapeutic Opportunity for Immune Cold Molecular Cancer SubtypesPaweł Karpiński0Łukasz Łaczmański1Maria M. Sąsiadek2Department of Genetics, Wroclaw Medical University, Wroclaw, PolandLaboratory of Genomics & Bioinformatics, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, PolandDepartment of Genetics, Wroclaw Medical University, Wroclaw, PolandCurrent immunotherapies are effective only in a subset of patients, likely due to several factors including defects in tumor cell antigen presentation, decreased response to immune effectors, and molecular heterogeneity of cancers. Recent molecular classifications enable the categorization of many tumor types. However, deregulation of major histocompatibility complex (MHC) gene expression is poorly characterized in the context of molecular cancer subtypes. To suppress the confounding effect of immune infiltrates on expression patterns of immunoregulators, we identified and removed genes with strong correlation to estimated immune compartment levels in each tumor type. Next, we reanalyzed a total of 13 TCGA cancer types encompassing 5651 tumors and 485 normal adjacent tissues by performing unsupervised clustering of 14 MHC genes. Subsequently, resultant clusters were statistically compared in terms of expression of other immune-related genes. Three MHC expression clusters were discovered by unsupervised clustering. We identified concordantly decreased expression of MHC genes (MHC-low) in 26 out of 55 molecular subtypes. Consequently, our study underlines the urgent need for designing strategies to enhance tumor MHC expression that could improve immune cold tumor rejection by cytotoxic T lymphocytes.http://dx.doi.org/10.1155/2020/8758090 |
| spellingShingle | Paweł Karpiński Łukasz Łaczmański Maria M. Sąsiadek Major Histocompatibility Complex Genes as Therapeutic Opportunity for Immune Cold Molecular Cancer Subtypes Journal of Immunology Research |
| title | Major Histocompatibility Complex Genes as Therapeutic Opportunity for Immune Cold Molecular Cancer Subtypes |
| title_full | Major Histocompatibility Complex Genes as Therapeutic Opportunity for Immune Cold Molecular Cancer Subtypes |
| title_fullStr | Major Histocompatibility Complex Genes as Therapeutic Opportunity for Immune Cold Molecular Cancer Subtypes |
| title_full_unstemmed | Major Histocompatibility Complex Genes as Therapeutic Opportunity for Immune Cold Molecular Cancer Subtypes |
| title_short | Major Histocompatibility Complex Genes as Therapeutic Opportunity for Immune Cold Molecular Cancer Subtypes |
| title_sort | major histocompatibility complex genes as therapeutic opportunity for immune cold molecular cancer subtypes |
| url | http://dx.doi.org/10.1155/2020/8758090 |
| work_keys_str_mv | AT pawełkarpinski majorhistocompatibilitycomplexgenesastherapeuticopportunityforimmunecoldmolecularcancersubtypes AT łukaszłaczmanski majorhistocompatibilitycomplexgenesastherapeuticopportunityforimmunecoldmolecularcancersubtypes AT mariamsasiadek majorhistocompatibilitycomplexgenesastherapeuticopportunityforimmunecoldmolecularcancersubtypes |