Tumor-infiltrating lymphocytes and PD-L1 expression in pre- and post-treatment ovarian cancer during neoadjuvant chemotherapy (254)

Abstract

Objectives: To investigate the dynamic changes of tumor immune microenvironment (TME) by evaluating lymphocyte infiltration before and after neoadjuvant chemotherapy (NACT) in patients with advanced-stage ovarian cancer. Methods: We conducted whole-transcriptome sequencing coupled with immunohistochemistry of 147 patients, including 140 pairs of serial tumor samples collected before NACT and at the time of interval debulking surgery (IDS). PD-L1 expression was determined by using a combined positive score (CPS). Tumor-infiltrating lymphocytes (TIL) were assessed by standardized methods according to the guidelines of the International TIL working group. Results: All the patients had high-grade serous carcinoma and were treated with platinum-based chemotherapy. High pre-NACT PD-L1 level (CPS ≥ 10%) was associated with worse progression-free survival (PFS, p < 0.001) and overall survival (OS, p = 0.038). High pre-NACT TIL level (>20%) was associated with better PFS (p = 0.039) and trend of better OS (p = 0.077). Post-NACT PD-L1 and TIL levels were not associated with survival outcomes. PD-L1 level (p = 0.001) and TIL level (p <0.001) were significantly increased before and after NACT. An increase in TIL in response to NACT was associated with shorter PFS compared to patients with decreased TIL levels (p = 0.020). A change in the PD-L1 level had no impact on the prognosis. In whole-transcriptome sequencing, stromal score (p = 8.6e-0.7), immune score (p = 4e-0.6), and CYT score (p = 2.1e-0.5) were significantly increased after NACT. Conclusions: Pre-NACT TIL level was associated with a survival benefit in advanced-stage ovarian cancer. By contrast, increased TIL level was an adverse prognostic factor for survival outcomes. Further research is needed to find a patient group that can benefit from immunotherapy in the NACT setting. Objectives: To investigate the dynamic changes of tumor immune microenvironment (TME) by evaluating lymphocyte infiltration before and after neoadjuvant chemotherapy (NACT) in patients with advanced-stage ovarian cancer. Methods: We conducted whole-transcriptome sequencing coupled with immunohistochemistry of 147 patients, including 140 pairs of serial tumor samples collected before NACT and at the time of interval debulking surgery (IDS). PD-L1 expression was determined by using a combined positive score (CPS). Tumor-infiltrating lymphocytes (TIL) were assessed by standardized methods according to the guidelines of the International TIL working group. Results: All the patients had high-grade serous carcinoma and were treated with platinum-based chemotherapy. High pre-NACT PD-L1 level (CPS ≥ 10%) was associated with worse progression-free survival (PFS, p < 0.001) and overall survival (OS, p = 0.038). High pre-NACT TIL level (>20%) was associated with better PFS (p = 0.039) and trend of better OS (p = 0.077). Post-NACT PD-L1 and TIL levels were not associated with survival outcomes. PD-L1 level (p = 0.001) and TIL level (p <0.001) were significantly increased before and after NACT. An increase in TIL in response to NACT was associated with shorter PFS compared to patients with decreased TIL levels (p = 0.020). A change in the PD-L1 level had no impact on the prognosis. In whole-transcriptome sequencing, stromal score (p = 8.6e-0.7), immune score (p = 4e-0.6), and CYT score (p = 2.1e-0.5) were significantly increased after NACT. Conclusions: Pre-NACT TIL level was associated with a survival benefit in advanced-stage ovarian cancer. By contrast, increased TIL level was an adverse prognostic factor for survival outcomes. Further research is needed to find a patient group that can benefit from immunotherapy in the NACT setting.