Adaptive immune response and PD-1/ PD-L1 status in chemotherapy treated high grade serous carcinoma is dependent on...

Platinum-based chemotherapy and debulking surgery is the standard of care for patients with advanced tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response scoring (CRS) system is a histopathologic scoring system developed to measure response to neoadjuvant chemotherapy with prognostic implications. Omental samples with high CRS have greater inflammatory cell infiltrates, but the immunophenotype of infiltrating immune cells and PD-L1 expression of the residual tumor has not been well-defined.

Twenty cases of patients with FIGO stage IIIA to IIIC HGSC undergoing interval debulking after receiving 3-4 rounds of chemotherapy were selected. 6/20 cases of omental samples were graded as CRS 1, 7/20 were graded CRS 2, and 7/20 were graded CRS 3. The following immunohistochemical stains were performed: CD8, CD4, Foxp3, PD1, and PD-L1. The total number of tumor-infiltrating lymphocytes was recorded, and each case was given a PD-L1 combined positive score (CPS) and tumor proportion score (TPS).

There was a significantly greater number of CD8⁺ T cells, PD-1+ T cells, CD4⁺ T cells, and Foxp3+ T cells in CRS 3-scored cases compared to CRS 1 scored cases (p-values: 0.0018, 0.0224, 0.0071, and 0.0136, respectively). CRS 3-scored cases had a greater PD-L1 CPS (CRS 3 CPS 13 ± 8.2 versus CRS 1 CPS 0 ± 0; p-value: 0.0485).

Tubo-ovarian high-grade serous carcinoma with greater response to neoadjuvant treatment have significantly greater T cell infiltrate and greater PD-L1 combined positive score, highlighting a potential role of the CRS as a predictive biomarker for immune checkpoint blockade therapy.