Tumor immune microenvironment and implications for progression and survival in patients with recurrent endometrial cancer (182)

Abstract

Objectives: The immunologic response to cancer influences disease progression and survival in ways that are not yet completely understood. The objective of this analysis was to understand markers of immune exhaustion and mismatch repair within the tumor immune microenvironment in patients with recurrent endometrial cancer. Methods: We identified patients matched with primary and recurrent endometrial adenocarcinoma at a single high-volume academic medical center. Histologic slides were reviewed to confirm the diagnosis of primary and recurrent cancer, and formalin-fixed paraffin-embedded tissue blocks were requested from archives. Immunohistochemistry (IHC) was performed using antibodies against CD3 and immune exhaustion markers (PD1, PDL1, CTLA4, TIM3, and TIGIT) to quantify the number of tumor-infiltrating lymphocytes (TILs). Peritumoral lymphocytes (PTLs) were evaluated in a semi-quantitative manner. Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS), and the log-rank test was used to compare between groups. Conclusions: Among patients with endometrial cancer who ultimately develop recurrent disease, the number of TILs and expression of immune exhaustion markers at initial diagnosis are not associated with PFS but are associated with OS. Specifically, the higher number of lymphocytes and increased expression of exhaustion markers PD1, PDL1, and TIGIT at the time of initial diagnosis are associated with decreased OS. Further work is needed to determine the prognostic value of immune exhaustion markers for patients who develop recurrent endometrial cancer. Objectives: The immunologic response to cancer influences disease progression and survival in ways that are not yet completely understood. The objective of this analysis was to understand markers of immune exhaustion and mismatch repair within the tumor immune microenvironment in patients with recurrent endometrial cancer. Methods: We identified patients matched with primary and recurrent endometrial adenocarcinoma at a single high-volume academic medical center. Histologic slides were reviewed to confirm the diagnosis of primary and recurrent cancer, and formalin-fixed paraffin-embedded tissue blocks were requested from archives. Immunohistochemistry (IHC) was performed using antibodies against CD3 and immune exhaustion markers (PD1, PDL1, CTLA4, TIM3, and TIGIT) to quantify the number of tumor-infiltrating lymphocytes (TILs). Peritumoral lymphocytes (PTLs) were evaluated in a semi-quantitative manner. Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS), and the log-rank test was used to compare between groups. Conclusions: Among patients with endometrial cancer who ultimately develop recurrent disease, the number of TILs and expression of immune exhaustion markers at initial diagnosis are not associated with PFS but are associated with OS. Specifically, the higher number of lymphocytes and increased expression of exhaustion markers PD1, PDL1, and TIGIT at the time of initial diagnosis are associated with decreased OS. Further work is needed to determine the prognostic value of immune exhaustion markers for patients who develop recurrent endometrial cancer.