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. |
---|---|
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. |
References: | Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch-repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–13. (PMID: 10.1126/science.aan6733) Makker V, Rasco D, Vogelzang NJ, Brose MS, Cohn AL, Mier J, et al. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019;20:711–8. (PMID: 10.1016/S1470-2045(19)30020-8) Zhao P, Li L, Jiang X, Li Q. Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy. J Hematol Oncol. 2019;12:54. (PMID: 10.1186/s13045-019-0738-1) Bestvina CM, Fleming GF. Chemotherapy for endometrial cancer in adjuvant and advanced disease settings. Oncologist. 2016;21:1250–9. (PMID: 10.1634/theoncologist.2016-0062) Ott PA, Bang YJ, Piha-Paul SA, Razak ARA, Bennouna J, Soria J, et al. T-cell–inflamed gene-expression profile, programmed death ligand 1 expression, and tumor mutational burden predict efficacy in patients treated with pembrolizumab across 20 cancers: KEYNOTE-028. J Clin Oncol. 2019;37:318–27. (PMID: 10.1200/JCO.2018.78.2276) Ott PA, Bang YJ, Berton-Rigaud D, Elez E, Pishvaian MJ, Rugo HS, et al. Safety and antitumor activity of pembrolizumab in advanced programmed death ligand 1–positive endometrial cancer: results from the KEYNOTE-028 study. J Clin Oncol. 2017;35:2535–41. Friedrich M, Jasinski-Bergner S, Lazaridou M-F, Subbarayan K, Massa C, Tretbar S, et al. Tumor-induced escape mechanisms and their association with resistance to checkpoint inhibitor therapy. Cancer Immunol Immunother. 2019;68:1689–1700. (PMID: 10.1007/s00262-019-02373-1) Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res. 2014;20:5064–74. (PMID: 10.1158/1078-0432.CCR-13-3271) Kloor M, Becker C, Benner A, Woerner SM, Gebert J, Ferrone S, et al. Immunoselective pressure and human leukocyte antigen class I antigen machinery defects in microsatellite unstable colorectal cancers. Cancer Res. 2005;65:6418–24. (PMID: 10.1158/0008-5472.CAN-05-0044) Neefjes J, Jongsma MLM, Paul P, Bakke O. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol. 2011;11:823–36. (PMID: 10.1038/nri3084) Mittica G, Genta S, Aglietta M, Valabrega G. Immune checkpoint inhibitors: a new opportunity in the treatment of ovarian cancer? Int J Mol Sci. 2016;17 https://doi.org/10.3390/ijms17071169. Bijen CBM, Bantema-Joppe EJ, de Jong RA, Leffers N, Mourits MJE, Eggink HF, et al. The prognostic role of classical and nonclassical MHC class I expression in endometrial cancer. Int J Cancer. 2010;126:1417–27. (PMID: 19728333) de Jong RA, Boerma A, Boezen HM, Mourits MJE, Hollema H, Nijman HW. Loss of HLA class I and mismatch repair protein expression in sporadic endometrioid endometrial carcinomas. Int J Cancer. 2012;131:1828–36. (PMID: 10.1002/ijc.27449) Šmahel M. PD-1/PD-L1 Blockade Therapy for Tumors with Downregulated MHC Class I Expression. Int J Mol Sci. 2017;18:1331. Kriegsman BA, Vangala P, Chen BJ, Meraner P, Bass AL, Garber M, et al. Frequent Loss of IRF2 in Cancers Leads to Immune Evasion through Decreased MHC Class I Antigen Presentation and Increased PD-L1 Expression. J Immunol. 2019;203:1999–2010. (PMID: 10.4049/jimmunol.1900475) Ugurel S, Spassova I, Wohlfarth J, Drusio C, Cherouny A, Melior A, et al. MHC class-I downregulation in PD-1/PD-L1 inhibitor refractory Merkel cell carcinoma and its potential reversal by histone deacetylase inhibition: a case series. Cancer Immunol Immunother. 2019;68:983–90. (PMID: 10.1007/s00262-019-02341-9) Yoo SH, Keam B, Ock C-Y, Kim S, Han B, Kim J-W, et al. Prognostic value of the association between MHC class I downregulation and PD-L1 upregulation in head and neck squamous cell carcinoma patients. Sci Rep. 2019;9:7680. (PMID: 10.1038/s41598-019-44206-2) Erdogdu IH. MHC Class 1 and PDL-1 Status of Primary Tumor and Lymph Node Metastatic Tumor Tissue in Gastric Cancers. Gastroenterol Res Pr. 2019;2019:4785098. Mills AM, Liou S, Ford JM, Berek JS, Pai RK, Longacre TA. Lynch syndrome screening should be considered for all patients with newly diagnosed endometrial cancer. Am J Surg Pathol. 2014;38:1501–9. (PMID: 10.1097/PAS.0000000000000321) Mills AM, Longacre TA. Lynch syndrome screening in the gynecologic tract: current state of the art. Am J Surg Pathol. 2016;40:e35–44. (PMID: 10.1097/PAS.0000000000000608) Kulangara K, Zhang N, Corigliano E, Guerreo L, Waldroup S, Jaiswal D, et al. Clinical Utility of the Combined Positive Score for Programmed Death Ligand-1 Expression and the Approval of Pembrolizumab for Treatment of Gastric Cancer. Arch Pathol Lab Med. 2019;143:330–7. (PMID: 10.5858/arpa.2018-0043-OA) Administration USF and D FDA approves pembrolizumab for advanced cervical cancer with disease progression during or after chemotherapy [Internet]. 2018. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm610572.htm . Chung HC, Ros W, Delord J-P, Perets R, Italiano A, Shapira-Frommer R, et al. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: results from the phase II KEYNOTE-158 Study. J Clin Oncol. 2019;37:1470–8. (PMID: 10.1200/JCO.18.01265) Sloan EA, Ring KL, Willis BC, Modesitt SC, Mills AM. PD-L1 Expression in Mismatch Repair-deficient Endometrial Carcinomas, Including Lynch Syndrome-associated and MLH1 Promoter Hypermethylated Tumors. Am J Surg Pathol. 2017;41:326–33. (PMID: 10.1097/PAS.0000000000000783) Friedman LA, Ring KL, Mills. AMLAG-3 and GAL-3 in endometrial carcinoma: emerging candidates for immunotherapy. Int J Gynecol Pathol. 2020;39:203–12. (PMID: 10.1097/PGP.0000000000000608) Moore M, Ring KL, Mills AM. TIM-3 in endometrial carcinomas: an immunotherapeutic target expressed by mismatch repair-deficient and intact cancers. Mod Pathol. 2019;32:1168–79. (PMID: 10.1038/s41379-019-0251-7) Mills AM, Zadeh S, Sloan EA, Chinn Z, Modesitt SC, Ring KL. Indoleamine 2,3-dioxygenase in endometrial cancer: a targetable mechanism of immune resistance in mismatch repair-deficient and intact endometrial carcinomas. Mod Pathol. 2018;31:1282–90. (PMID: 10.1038/s41379-018-0039-1) Friedman L, Ring K. Mills ALAG-3 and GAL-3 in endometrial carcinoma: emerging candidates for immunotherapy. Int J Gynecol Pathol. 2019;39:203–12. (PMID: 10.1097/PGP.0000000000000608) Howitt BE, Shukla SA, Sholl LM, Ritterhouse LL, Watkins JC, Rodig S, et al. Association of Polymerase e-Mutated and Microsatellite-Instable Endometrial Cancers With Neoantigen Load, Number of Tumor-Infiltrating Lymphocytes, and Expression of PD-1 and PD-L1. JAMA Oncol. 2015;1:1319–23. (PMID: 10.1001/jamaoncol.2015.2151) Konstantinopoulos PA, Luo W, Liu JF, Gulhan DC, Krasner C, Ishizuka JJ, et al. Phase II study of avelumab in patients with mismatch repair deficient and mismatch repair proficient recurrent/persistent endometrial cancer. J Clin Oncol. 2019;37:2786–94. (PMID: 10.1200/JCO.19.01021) Oaknin A, Duska LR, Sullivan RJ, Pothuri B, Ellard SL, Leath CA, et al. Preliminary safety, efficacy, and pharmacokinetic/pharmacodynamic characterization from GARNET, a phase I/II clinical trial of the anti–PD-1 monoclonal antibody, TSR-042, in patients with recurrent or advanced MSI-h and MSS endometrial cancer. Gynecol Oncol. 2019;154:17. (PMID: 10.1016/j.ygyno.2019.04.044) Rubinstein MM, Makker V. Optimizing immunotherapy for gynecologic cancers. Curr Opin Obstet Gynecol. 2020;32:1–8. (PMID: 10.1097/GCO.0000000000000603) Marcus A, Gowen BG, Thompson TW, Iannello A, Ardolino M, Deng W, et al. Recognition of tumors by the innate immune system and natural killer cells. Adv Immunol. 2014;122:91–128. Degos C, Heinemann M, Barrou J, Boucherit N, Lambaudie E, Savina A, et al. Endometrial tumor microenvironment alters human NK cell recruitment, and resident NK cell phenotype and function. Front Immunol. 2019;10:877. (PMID: 10.3389/fimmu.2019.00877) Abel AM, Yang C, Thakar MS, Malarkannan S. Natural killer cells: development, maturation, and clinical utilization. Front Immunol. 2018;9:1869. (PMID: 10.3389/fimmu.2018.01869) Hu W, Wang G, Huang D, Sui M, Xu Y. Cancer immunotherapy based on natural killer cells: current progress and new opportunities. Front Immunol. 2019;10:1331. Perea F, Sánchez-Palencia A, Gómez-Morales M, Bernal M, Concha A, Garcia MM, et al. HLA class I loss and PD-L1 expression in lung cancer: Impact on T-cell infiltration and immune escape. Oncotarget. 2018;9:4120–33. (PMID: 10.18632/oncotarget.23469) Umemoto Y, Okano S, Matsumoto Y, Nakagawara H, Matono R, Yoshiya S, et al. Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy. J Gastroenterol. 2014;50:65–75. (PMID: 10.1007/s00535-014-0933-3) Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med. 2016;375:819–29. (PMID: 10.1056/NEJMoa1604958) Mills AM, Peres LC, Meiss A, Ring KL, Modesitt SC, Abbott SE, et al. Targetable Immune Regulatory Molecule Expression in High-Grade Serous Ovarian Carcinomas in African American Women: a Study of PD-L1 and IDO in 112 Cases From the African American Cancer Epidemiology Study (AACES). Int J Gynecol Pathol. 2019;38:157–70. (PMID: 10.1097/PGP.0000000000000494) Chinn Z, Stoler MH, Mills AM. PD-L1 and IDO expression in cervical and vulvar invasive and intraepithelial squamous neoplasias: implications for combination immunotherapy. Histopathology. 2019;74:256–68. (PMID: 10.1111/his.13723) Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, et al. Fulminant Myocarditis with Combination Immune Checkpoint Blockade. N Engl J Med. 2016;375:1749–55. (PMID: 10.1056/NEJMoa1609214) Läubli H, Balmelli C, Bossard M, Pfister O, Glatz K, Zippelius A. Acute heart failure due to autoimmune myocarditis under pembrolizumab treatment for metastatic melanoma. J Immunother Cancer. 2015;3:11–015-0057-1. eCollection 2015. (PMID: 10.1186/s40425-015-0057-1) Cappelli LC, Gutierrez AK, Bingham CO 3rd, Shah AA. Rheumatic and musculoskeletal immune-related adverse events due to immune checkpoint inhibitors: a systematic review of the literature. Arthritis Care Res (Hoboken). 2017;69:1751–63. (PMID: 10.1002/acr.23177) Groisberg R, Hong DS, Behrang A, Hess K, Janku F, Piha-Paul S, et al. Characteristics and outcomes of patients with advanced sarcoma enrolled in early phase immunotherapy trials. J Immunother Cancer. 2017;5:100-017-0301-y. (PMID: 10.1186/s40425-017-0301-y) The Value and Cost of Immunotherapy Cancer Treatments [Internet]. [cited 5 February 2020]. https://www.healthline.com/health-news/value-and-cost-of-immunotherapy#2 . |
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 |
تدمد: | 1530-0285 |
---|---|
DOI: | 10.1038/s41379-020-00682-w |