Abstract A038: Targeting TCTP overcomes resistance to T cell-mediated immunotherapy by reversing the multi-malignant phenotypes of immune-refractory tumor cells

Abstract

Abstract Cancer immunotherapy, particularly T cell-mediated therapy such as immune checkpoint blockade (ICB) and adoptive T cell transfer (ACT), has shifted the paradigm for cancer treatment. However, the emergence of immune-refractory tumor has limited its clinical success by disrupting one or more steps of the cancer immunity cycle. In addition, multi-malignant phenotypes of immune-refractory tumor cells are also one of the major causes result poor prognosis of patients. We need to identify novel predictive biomarker allowing for the selection of patients who will receive clinical benefit from immune-refractory tumors. Therefore, identifying the immune-resistance and multi-malignant factor, which not only can be targeted by clinically available medicines is very important. Here, we identified TCTP as a novel factor conferring multi-malignant phenotypes of immune-refractory tumor cells. We discovered a vital role of TCTP at the crossroads between multi-malignant tumor cells and the anti-cancer immunity system by demonstrating that TCTPhigh tumor cells enriched by immune selection pressure drive immune-refractory phenotypes. Importantly, the expression levels of TCTP within the tumors significantly associated with the clinical response of anti-PD-L1 therapy, which suggest TCTP as a prognostic marker in the case of clinical trials. Furthermore, targeting TCTP by clinical available drug overcomes the resistance to T cell-mediated therapy including ICB and ACT. Thus, our findings demonstrated that TCTP could be a both a valid target a prognostic marker providing a framework for patient selection to apply combined therapy of T cell-mediated therapy with TCTP-targeting drugs. Citation Format: Tae Woo Kim. Targeting TCTP overcomes resistance to T cell-mediated immunotherapy by reversing the multi-malignant phenotypes of immune-refractory tumor cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A038.