دورية أكاديمية
MHC class I loss in endometrial carcinoma: a potential resistance mechanism to immune checkpoint inhibition.
| العنوان: | MHC class I loss in endometrial carcinoma: a potential resistance mechanism to immune checkpoint inhibition. |
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| المؤلفون: | Friedman LA; Department of Pathology, University of Virginia, Charlottesville, VA, USA., Bullock TN; Department of Pathology, University of Virginia, Charlottesville, VA, USA., Sloan EA; Department of Pathology, Georgetown University, Washington, DC, USA., Ring KL; Department of Obstetrics and Gynecology, University of Virginia, Charlottesville, VA, USA., Mills AM; Department of Pathology, University of Virginia, Charlottesville, VA, USA. amm7r@virginia.edu. |
| المصدر: | Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2021 Mar; Vol. 34 (3), pp. 627-636. Date of Electronic Publication: 2020 Oct 03. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc Country of Publication: United States NLM ID: 8806605 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-0285 (Electronic) Linking ISSN: 08933952 NLM ISO Abbreviation: Mod Pathol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2023- : [New York] : Elsevier Inc. Original Publication: Baltimore, MD : Williams & Wilkins, c1988- |
| مواضيع طبية MeSH: | Drug Resistance, Neoplasm*, B7-H1 Antigen/*antagonists & inhibitors , Biomarkers, Tumor/*analysis , Carcinoma/*immunology , Endometrial Neoplasms/*immunology , Histocompatibility Antigens Class I/*analysis , Immune Checkpoint Inhibitors/*therapeutic use, B7-H1 Antigen/analysis ; CD3 Complex/analysis ; Carcinoma/drug therapy ; Carcinoma/pathology ; Clinical Decision-Making ; DNA Mismatch Repair ; Endometrial Neoplasms/drug therapy ; Endometrial Neoplasms/pathology ; Female ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating/immunology ; Predictive Value of Tests ; Tumor Microenvironment/immunology |
| مستخلص: | Major histocompatibility complex (MHC) class I is a membrane-bound protein complex expressed on nucleated human cells. MHC class I presents intracellular protein fragments to cytotoxic T cells and triggers an activation cascade upon neoantigen detection by these cells. MHC class I loss by tumor cells decreases tumor neoantigen presentation to the immune system and therefore represents a possible mechanism of immunotherapeutic resistance even among cancers that otherwise appear to be good candidates for checkpoint inhibition, such as mismatch repair (MMR)-deficient and PD-L1-positive malignancies. We herein assess MHC class I expression in a range of endometrial carcinomas, including MMR-deficient and PD-L1-positive cancers. Immunohistochemical staining for combined MHC class I A-, B-, and C-heavy chains was performed on 76 cases of endometrial carcinoma and was classified as present, subclonally lost, or diffusely lost. Tumoral PD-L1 expression, PD-L1 combined positive score, and CD3-positive T lymphocytes were also quantified. Forty-two percent of tumors showed loss of MHC class I expression, either in a subclonal (26%) or diffuse (16%) pattern. This included 46% of MMR-deficient and 25% of PD-L1-positive cancers. These findings suggest that tumoral MHC class I status may be an important factor to consider when selecting endometrial cancer patients for checkpoint inhibition. |
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| المشرفين على المادة: | 0 (B7-H1 Antigen) 0 (Biomarkers, Tumor) 0 (CD274 protein, human) 0 (CD3 Complex) 0 (Histocompatibility Antigens Class I) 0 (Immune Checkpoint Inhibitors) |
| تواريخ الأحداث: | Date Created: 20201004 Date Completed: 20211103 Latest Revision: 20230210 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1038/s41379-020-00682-w |
| PMID: | 33011747 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1530-0285 |
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| DOI: | 10.1038/s41379-020-00682-w |