Abstract P4-06-27: LncRNA NKILA promotes tumour immune evasion by sensitizing tumour-specific t cells to activation-induced cell death

Abstract

Abstract Activation induced cell death (AICD) of T lymphocytes is critical to maintain T-cell homeostasis, which is adopted by malignant tumors to convey immune evasion by eliminating tumor-reactive cytotoxic T cells. In this study, we demonstrated excessive apoptosis of tumor antigen-specific CTLs in breast and lung cancers. However, the mechanism involved in AICD of tumor-specific T cells remains obscure. Here, we demonstrated that NF-κB activity in tumor-specific T cells is high at the early phase of CTL activation induced by breast tumor antigens, but is suppressed at the later phase. This results in massive apoptosis of tumor-specific CTLs challenged by tumor cells. Interestingly, NKILA, an NFκB interacting lncRNA, sensitizes CTLs to AICD by inhibiting NF-κB activities after their activation, leading to tumor immune evasion. In vivo, administering CTLs with NKILA silencing into immunocompromised mice with breast cancer patient derived xenografts (PDXs) effectively inhibits PDX growth by increasing CTL infiltration. Clinically, NKILA was overexpressed in the tumor specific CTLs of breast and lung cancers, which was associated with less CTL infiltration in the tumors and shorter patient survival. Our findings present the first evidence that AICD in tumor-specific CTLs is crucial to cancer immune evasion, and targeting NKILA in CTLs emerges as a novel anti-tumor immunotherapy. Citation Format: Song E, Su S, Huang D. LncRNA NKILA promotes tumour immune evasion by sensitizing tumour-specific t cells to activation-induced cell death [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-06-27.