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- W4313373863 abstract "Abstract Head and neck cancer (HNC) is the sixth most common cancer worldwide with a five-year survival of 50%. Immunotherapy is emerging as a promising treatment modality in HNC. Pembrolizumab, an anti-PD-1 antibody, is an immunotherapy currently approved in metastatic HNC and in clinical trials for curative intent. Although there are promising responses to Pembrolizumab, its effect on cytotoxic CD8+ T cell function is not understood. T cell cytotoxicity is critically important in the elimination of tumors and in the tumor microenvironment, cytotoxicity depends on ion channel activity which is defective in HNC patients. Therefore, to elucidate mechanisms of Pembrolizumab, we studied potassium channel (KCa3.1 and Kv1.3) functionality and Ca2+ fluxes in CD8+ peripheral blood T cells (PBTs) of naïve HNC patients before/after Pembrolizumab treatment (n=22) as well as tumor infiltrating lymphocytes (TILs) functionality. Untreated HNC patients were controls (n= 13). Pembrolizumab-treated patients were categorized as responders (R) or non-responders (NR) based on pathological response. We then performed electrophysiological and Ca2+ flux experiments. We observed that Pembrolizumab increased KCa3.1 currents in PBTs (29.8%, p=0.026). Moreover, after treatment, R PBTs also had increases in Kv1.3 currents and Ca2+ fluxes (22.1%, p=0.047; 16.5%, p<0.001; respectively). In TILs, Kv1.3 currents and Ca2+ fluxes were increased in Pembrolizumab-treated patients (64%, p=0.002; 34.8%, p=0.004; respectively). These data show that Pembrolizumab increases the fitness of CD8+PBTs and TILs in relation to ion channel functionality, especially in R, and thus could lead to better understanding of the Pembrolizumab mechanism of action/resistance." @default.
- W4313373863 created "2023-01-06" @default.
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- W4313373863 date "2020-05-01" @default.
- W4313373863 modified "2023-09-27" @default.
- W4313373863 title "Pembrolizumab treatment increases K+ channel function and calcium fluxes in cytotoxic T cells of head and neck cancer patients" @default.
- W4313373863 doi "https://doi.org/10.4049/jimmunol.204.supp.165.41" @default.
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