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Dynamics of the Tumor Immune Microenvironment during Neoadjuvant Chemotherapy of High-Grade Serous Ovarian Cancer

 Yong Jae Lee  ;  Ha Young Woo  ;  Yoo-Na Kim  ;  Junsik Park  ;  Eun Ji Nam  ;  Sang Wun Kim  ;  Sunghoon Kim  ;  Young Tae Kim  ;  Eunhyang Park  ;  Je-Gun Joung  ;  Jung-Yun Lee 
 CANCERS, Vol.14(9) : 2308, 2022-05 
Journal Title
Issue Date
high grade serous ovarian cancer ; immune checkpoint inhibitors ; neoadjuvant chemotherapy ; tumor immune microenvironment ; tumor-infiltrating lymphocytes
The dynamic changes in the tumor immune microenvironment (TIME) triggered by neoadjuvant chemotherapy (NAC) have not been clearly defined in advanced-stage ovarian cancer. We analyzed the immunologic changes induced by NAC to correlate them with clinical outcomes. We compared the changes in the immune infiltration of high-grade serous carcinoma biopsies before and after NAC via immunohistochemistry (147 paired samples) and whole transcriptome sequencing (35 paired samples). Immunohistochemistry showed significantly increased PD-L1 levels and TIL levels after NAC. Whole transcriptome sequencing revealed that the stromal score, immune score, and cytolytic activity score significantly increased after NAC. An increased tumor-infiltrating lymphocyte (TIL) level in response to NAC was associated with shorter progression-free survival compared with decreased TIL level after NAC. In tumors with increased TIL levels after NAC, the relative fraction of CD8 T cells and regulatory T cells significantly increased with immunohistochemistry. Post-NAC tumors were enriched in gene sets associated with immune signaling pathways, such as regulatory T cell and JAK/STAT signaling pathways. NAC induced dynamic changes in the TIME that increased TIL levels, but their high abundance did not impart any survival benefit. Our data may provide therapeutic strategies to improve the survival benefit from immunotherapies in ovarian cancer.
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1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sang Wun(김상운) ORCID logo https://orcid.org/0000-0002-8342-8701
Kim, Sung Hoon(김성훈) ORCID logo https://orcid.org/0000-0002-1645-7473
Kim, Young Tae(김영태) ORCID logo https://orcid.org/0000-0002-7347-1052
Kim, Yoo‐Na(김유나)
Nam, Eun Ji(남은지) ORCID logo https://orcid.org/0000-0003-0189-3560
Park, Eunhyang(박은향) ORCID logo https://orcid.org/0000-0003-2658-5054
Lee, Yong Jae(이용재) ORCID logo https://orcid.org/0000-0003-0297-3116
Lee, Jung-Yun(이정윤) ORCID logo https://orcid.org/0000-0001-7948-1350
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