透明细胞癌是东亚地区（尤其是日本）卵巢癌的一种常见组织学类型，以其对化疗药物的耐药性和预后不良而闻名。 ARID1A 基因突变常见于卵巢透明细胞癌 (OCCC)，有助于其发病机制。最近的数据显示 ARID1A 突变与癌症免疫治疗的更好结果有关。因此，本研究旨在探讨携带ARID1A突变的OCCC的免疫治疗敏感性。使用免疫印迹法分析卵巢癌细胞系中ARID1A的表达。 OCCC 细胞系 JHOC-9 和 RMG-V 经过工程改造，可过表达 NY-ESO-1、HLA-A*02:01 和 ARID1A。与 ARID1A 缺陷的野生型细胞相比，在 ARID1A 恢复的细胞中评估了对化疗和对 NY-ESO-1 特异性的 T 细胞受体转导 T (TCR-T) 细胞的敏感性。JHOC-9 细胞和 RMG-V 细胞显示ARID1A蛋白无表达。 JHOC-9 和 RMG-V 细胞中 ARID1A 的过度表达不会影响对吉西他滨的敏感性。虽然 ARID1A 过表达降低了 RMG-V 细胞对顺铂的敏感性，但在 JHOC-9 细胞中没有这种作用。通过 IFNγ ESLIPOT 测定观察到，ARID1A 过表达降低了 NY-ESO-1 特异性 TCR-T 细胞的反应性。癌症免疫疗法是针对 ARID1A 缺陷的卵巢透明细胞癌的有效方法。版权所有 © 2024，国际研究所抗癌研究中心（George J. Delinasios 博士），保留所有权利。

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.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.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.Cancer immunotherapy is an effective approach to target ARID1A-deficient clear cell carcinoma of the ovary.Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.