Restoration of ARID1A Protein in ARID1A-deficient Clear Cell Carcinoma of the Ovary Attenuates Reactivity to Cytotoxic T Lymphocytes.

IF 2.6 4区医学 Q2 GENETICS & HEREDITY Cancer Genomics & Proteomics Pub Date : 2024-07-01 DOI:10.21873/cgp.20460

Risa Tsunematsu, Aiko Murai, Yuka Mizue, Terufumi Kubo, Tasuku Mariya, Rena Morita, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Tsuyoshi Saito, Toshihiko Torigoe

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Abstract

Background/aim: Clear cell carcinoma is a prevalent histological type of ovarian cancer in East Asia, particularly in Japan, known for its resistance to chemotherapeutic agents and poor prognosis. ARID1A gene mutations, commonly found in ovarian clear cell carcinoma (OCCC), contribute to its pathogenesis. Recent data revealed that the ARID1A mutation is related to better outcomes of cancer immunotherapy. Thus, this study aimed to investigate the immunotherapy treatment susceptibility of OCCC bearing ARID1A mutations.

Materials and methods: Expression of ARID1A was analyzed using western blotting in ovarian cancer cell lines. OCCC cell lines JHOC-9 and RMG-V were engineered to overexpress NY-ESO-1, HLA-A*02:01, and ARID1A. Sensitivity to chemotherapy and T cell receptor-transduced T (TCR-T) cells specific for NY-ESO-1 was assessed in ARID1A-restored cells compared to ARID1A-deficient wild-type cells.

Results: JHOC-9 cells and RMG-V cells showed no expression of ARID1A protein. Overexpression of ARID1A in JHOC-9 and RMG-V cells did not impact sensitivity to gemcitabine. While ARID1A overexpression decreased sensitivity to cisplatin in RMG-V cells, it had no such effect in JHOC-9 cells. ARID1A overexpression reduced the reactivity of NY-ESO-1-specific TCR-T cells, as observed by the IFNγ ESLIPOT assay.

Conclusion: Cancer immunotherapy is an effective approach to target ARID1A-deficient clear cell carcinoma of the ovary.

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在 ARID1A 基因缺陷的卵巢透明细胞癌中恢复 ARID1A 蛋白可减轻对细胞毒性 T 淋巴细胞的反应。

背景/目的：透明细胞癌是东亚（尤其是日本）一种常见的卵巢癌组织学类型，以对化疗药物耐药和预后不良而闻名。卵巢透明细胞癌（OCCC）中常见的 ARID1A 基因突变是其发病机制之一。最近的数据显示，ARID1A基因突变与癌症免疫疗法的良好疗效有关。因此，本研究旨在探讨ARID1A突变的卵巢透明细胞癌对免疫治疗的易感性：采用免疫印迹法分析 ARID1A 在卵巢癌细胞系中的表达。卵巢癌细胞株JHOC-9和RMG-V被设计为过表达NY-ESO-1、HLA-A*02:01和ARID1A。与 ARID1A 缺失的野生型细胞相比，评估了 ARID1A 恢复细胞对化疗和 NY-ESO-1 特异性 T 细胞受体转导 T（TCR-T）细胞的敏感性：结果：JHOC-9细胞和RMG-V细胞没有表达ARID1A蛋白。在JHOC-9和RMG-V细胞中过表达ARID1A不会影响对吉西他滨的敏感性。ARID1A的过表达降低了RMG-V细胞对顺铂的敏感性，但在JHOC-9细胞中却没有这种影响。通过IFNγ ESLIPOT试验观察到，ARID1A过表达降低了NY-ESO-1特异性TCR-T细胞的反应性：癌症免疫疗法是一种针对ARID1A缺陷卵巢透明细胞癌的有效方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Genomics & Proteomics ONCOLOGY-GENETICS & HEREDITY

CiteScore

5.00

自引率

8.00%

发文量

期刊介绍： Cancer Genomics & Proteomics (CGP) is an international peer-reviewed journal designed to publish rapidly high quality articles and reviews on the application of genomic and proteomic technology to basic, experimental and clinical cancer research. In this site you may find information concerning the editorial board, editorial policy, issue contents, subscriptions, submission of manuscripts and advertising. The first issue of CGP circulated in January 2004. Cancer Genomics & Proteomics is a journal of the International Institute of Anticancer Research. From January 2013 CGP is converted to an online-only open access journal. Cancer Genomics & Proteomics supports (a) the aims and the research projects of the INTERNATIONAL INSTITUTE OF ANTICANCER RESEARCH and (b) the organization of the INTERNATIONAL CONFERENCES OF ANTICANCER RESEARCH.