Abstract
Abstract Cancer immunotherapy, particularly T cell-mediated therapy such as immune checkpoint blockade (ICB) and adoptive T cell transfer (ACT), has emerged as a potentially powerful approach to cancer treatment. However, immunotherapeutic resistance limits 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. Therefore, identifying the immune-resistance and multi-malignant factor, which not only can be targeted by clinically available medicines it can also be a prognostic marker, is needed ideally. Here, we identified TCTP as a novel factor conferring multi-malignant phenotypes of immune-refractory tumor cells. We discovered a crucial 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 levels of TCTP within the tumors significantly correlated with the clinical outcome of anti-PD-L1 therapy, which demonstrate TCTP as a prognostic marker in the case of clinical trials. Furthermore, targeting TCTP by clinical available drug enhanced the response to T cell-mediated therapy including ICB and ACT. Thus, our findings emphasize 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 agents. Citation Format: Hyo-Jung Lee, Tae Woo Kim. Targeting TCTP reverses the multi-malignant phenotypes of immune-refractory tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6440.
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