Exploration of novel molecular targeted therapies based on tumor microenvironmental profile in endometrial cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16829
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: University of Tsukuba
• Principal Investigator: Shikama Ayumi 筑波大学, 医学医療系, 講師 (40778627)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 子宮内膜癌 / 腫瘍微小環境

Outline of Final Research Achievements

The aim of our study was to investigate the precise prognostic significance of the Tumor microenvironment (TME) profile in endometrial carcinoma. We performed immunohistochemistry of the TME proteins, PD-L1, PD-1, CD4, CD8, CD68, and VEGF in endometrial carcinomas from 221 patients. High PD-L1 in tumor cells (TCs) was associated with better OS, whereas high PD-L1 in tumor-infiltrating immune cells (TICs) was associated with worse OS. Univariate and multivariate analyses of prognostic factors revealed that high PD-L1 in TCs and high density of CD4+ TICs were significant and independent for favorable OS. The current findings indicate that PD-L1 and CD4+ helper T cells may be reasonable targets for improving survival through manipulating chemosensitivity, providing significant implications for combining immunotherapies into the therapeutic strategy for endometrial carcinoma.

Free Research Field

婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

子宮内膜癌における腫瘍微小環境と予後との関連性の調査結果より、PD-L1とCD4陽性ヘルパーT細胞が化学療法感受性に関与すること、PD/PD-L1を介した免疫チェックポイント機構が、子宮内膜癌での腫瘍微小環境を調節することにより。予後を改善する可能性があることが示唆された。このことは、選択肢の少ない子宮内膜癌の治療戦略において、免疫チェックポイント阻害剤を組み合わせる治療の可能性を拡大する上で重要な知見となったと考えられる。