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Abstract：
OBJECTIVE: 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.
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.
CONCLUSIONS: Cancer immunotherapy is an effective approach to target ARID1A-deficient clear cell carcinoma of the ovary.
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.
CONCLUSIONS: Cancer immunotherapy is an effective approach to target ARID1A-deficient clear cell carcinoma of the ovary.
摘要：
目的：透明细胞癌是东亚卵巢癌的一种常见组织学类型，尤其是在日本,以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的免疫治疗易感性.
方法:使用蛋白质印迹法分析ARID1A在卵巢癌细胞系中的表达。将OCCC细胞系JHOC-9和RMG-V工程化以过表达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特异的T细胞受体转导的T（TCR-T）细胞的敏感性。
结果：JHOC-9细胞和RMG-V细胞无ARID1A蛋白表达。ARID1A在JHOC-9和RMG-V细胞中的过表达不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，它在JHOC-9细胞中没有这种作用。ARID1A过表达降低NY-ESO-1特异性TCR-T细胞的反应性,通过IFNγESLIPOT测定观察到。
结论：癌症免疫治疗是靶向ARID1A缺乏的卵巢透明细胞癌的有效方法。
方法:使用蛋白质印迹法分析ARID1A在卵巢癌细胞系中的表达。将OCCC细胞系JHOC-9和RMG-V工程化以过表达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特异的T细胞受体转导的T（TCR-T）细胞的敏感性。
结果：JHOC-9细胞和RMG-V细胞无ARID1A蛋白表达。ARID1A在JHOC-9和RMG-V细胞中的过表达不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，它在JHOC-9细胞中没有这种作用。ARID1A过表达降低NY-ESO-1特异性TCR-T细胞的反应性,通过IFNγESLIPOT测定观察到。
结论：癌症免疫治疗是靶向ARID1A缺乏的卵巢透明细胞癌的有效方法。
