Abstract 5966: Cathepsin S mediates interleukin 7 to sculpture the tumor immunity in head and neck cancer

Abstract

Abstract Cathepsin S (CTSS) is a lysosomal enzyme that belongs to cysteine proteases. It is associated with progression of different types of cancer, mediating the antigen presentation, extracellular matrix degradation, angiogenesis, and metastasis. In recent studies, CTSS was suggested as a therapeutic target for cancer treatment. We found that, with a CTSS inhibitor RJW-58 treatment over tumor-bearing mouse, the serum showed an enhanced anti-tumor cytokine releasing of interleukin 7 (IL-7). In the mRNA array results of 40 pair head and neck patients’ sample, we found the negative correlation between CTSS and IL-7 comparing to the normal head and neck tissue. Moreover, we also found that the level of CD8 T cell infiltration is negatively correlated with the expression of CTSS in 20 head and neck cancer patients’ slides. In cell model, targeting CTSS by siRNA or RJW-58 promoted IL-7 secretion in different head and neck cancer cell lines. We demonstrated that cathepsin S decreased the secretion level of IL-7 through downregulating IL-7 receptor, a receptor that mediating IL-7 secretion, protein expression level resulting in activating lysosomal degradation pathway. Promoting cell proliferation of activated CD8 T cells was proved when CD8 T cells were treated with the condition medium from CTSS-knockdown head and neck cancer cells. In conclusion, this is the first study demonstrated that CTSS acted as a negative regulator in mediating IL-7 resulting in inducing an immune cell-suppressed microenvironment in head and neck cancer cells. (This work is supported by the NSTC grand number: MOST 110-2314-B-400-035) Citation Format: Yung-Chieh Chang, Shan-Hung Chen, Kwang-Yu Chang, Jang-Yang Chang. Cathepsin S mediates interleukin 7 to sculpture the tumor immunity in head and neck cancer [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 5966.