Abstract P5-04-28: Targeting TIGIT and PD-1 in triple negative breast cancer

Abstract

Abstract Background: Triple negative breast cancer is aggressive and has poor prognosis. Tumor infiltrating lymphocytes (TILs) have a prognostic value in triple negative breast cancer. Increased TILs are associated with better disease-free survival and overall survival in triple negative breast cancer (TNBC). Newly approved immunotherapy drug for metastatic triple negative breast cancer patients, Atezolizumab, has shown 10 months improvement in overall survival in for PD-L1 positive group in combination with nab-paclitaxel compared to placebo and paclitaxel. Beyond PD-1 inhibitors, there is a need to improve immunotherapy options in TNBC. TIGIT gene expression in triple negative breast cancer is associated with immune function is linked with improved relapse free survival and overall survival. CD155, a high affinity receptor for TIGIT, is expressed on tumor cells including lung and melanoma. We aim to evaluate the role of TIGIT in regulating immune response to TNBC, TIGIT cooperation with PD-1 in impeding T cell responses to TNBC, and expression of TIGIT ligands on TNBC. Methods: Fresh TNBC tumor samples were obtained from 10 untreated patients and were used for single cell suspension and multi parameter flow cytometry. Results: CD8+ and CD4+ TILs in TNBC exhibited higher PD-1 and TIGIT, yet lower CD226 expression as compared to circulating T cells. LAG-3 and TIM3 were expressed at low frequency in CD 8+ and CD 4+ cells. TNBC Tregs display high expression of TIGIT, PD-1, TIM3 but low CD226 expression. TIGIT interacts with CD155 and CD112 with high affinity and both were found to be highly expressed by TNBC tumor cells and APCs. PD-1−TIGIT+ CD8+ TILs are present at high frequency and appear to represent an activated T cell subset. PD-1+Tim-3+TIGIT+ produced less cytokines including interferon gamma, IL-2, and TNF than other CD8+ T cell subsets, representing a dysfunctional T cell subset. Conclusions: TIGIT is highly upregulated by TNBC CD8+ and CD4+ TILs while the TIGIT ligands are highly expressed by tumor cells and APCs in TNBC. In sharp contrast with metastatic melanoma, high frequency PD-1−TIGIT+CD8+ TILs are present in TNBC. Additional studies will investigate the role of dual PD-1/TIGIT blockade in increasing CD8+ TIL function in TNBC. Such data may support the dual PD-1/TIGIT blockade in TNBCs. Citation Format: Apurva Kumari Pandey, Joe Marc Chauvin, Adam Brufsky, Ornella Pagliano, Mignane Ka, Carmine Menna, Priscilla McAuliffe, Hassane Zarour. Targeting TIGIT and PD-1 in triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-28.