Changes in the tumor immune microenvironment during disease progression in clear cell ovarian cancer

FOXP3型 肿瘤微环境 医学 CD8型 免疫疗法 免疫系统 ARID1A型 癌症研究 卵巢癌 T细胞 PD-L1 免疫组织化学 细胞毒性T细胞 透明细胞癌 肿瘤浸润淋巴细胞 肿瘤科 内科学 癌症 免疫学 生物 突变 基因 体外 生物化学
作者
Ha Young Woo,Nayeon Kim,Jae Kwan Jun,Junsik Park,Eun Ji Nam,Sang Wun Kim,Sunghoon Kim,Young Tae Kim,Yong Jae Lee
出处
期刊:International Journal of Gynecological Cancer [BMJ]
卷期号:: ijgc-005662
标识
DOI:10.1136/ijgc-2024-005662
摘要

Objective The tumor immune microenvironment in ovarian clear cell carcinoma has not been clearly defined. We analyzed the immunological changes from treatment-naive to recurrence to correlate them with clinical outcomes. Method We compared the changes in immune infiltration of advanced-stage ovarian clear cell carcinoma samples before treatment and at the time of recurrence via immunohistochemistry (Programmed Cell Death-ligand 1 (PD-L1), cluster of differentiation 8 (CD8+), forkhead box P3 (Foxp3+)), tumor-infiltrating lymphocytes (TIL), and next-generation sequencing (54 patients). We analyzed the association between platinum sensitivity status and tumor immune microenvironment. Results Immunohistochemistry revealed significantly increased PD-L1 (p=0.048) and CD8+T cells (p=0.022) expression levels after recurrence. No significant differences were observed in TIL density or Foxp3+T cells. There was no significant correlation between TIL, PD-L1, CD8+T cell, and Foxp3+T cell levels in treatment-naive tumors and survival outcomes. The most common genomic alterations were PIK3CA (41.7%) and ARID1A (41.7%) mutations. There were no differences in the immunological changes or survival outcomes according to PIK3CA and ARID1A mutations. Patients with recurrent platinum-sensitive disease showed higher TIL expression levels. There were no significant differences in PD-L1, CD8+T cells, or Foxp3+T cells between platinum-sensitive and platinum-resistant diseases. Conclusion We characterized the tumor immune microenvironment in patients with advanced-stage ovarian clear cell carcinoma. PD-L1 and CD8+T cell expression significantly increased after recurrence. Whether this could be used to select patients for immunotherapy in the recurrence setting should be investigated.
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