CD8⁺ T cells play a role in the suppression of tumor growth and immunotherapy. Ion channels control the Ca²⁺-dependent function of CD8⁺ lymphocytes such as cytokine/granzyme production and tumor killing. Kv1.3 and KCa3.1 K⁺ channels stabilize the negative membrane potential of T cells to maintain Ca²⁺ influx through CRAC channels. We assessed the expression of Kv1.3, KCa3.1 and CRAC in CD8⁺ cells from ovarian cancer (OC) patients (n = 7). We found that the expression level of Kv1.3 was higher in patients with malignant tumors than in control or benign tumor groups while the KCa3.1 activity was lower in the malignant tumor group as compared to the others. We demonstrated that the Ca²⁺ response in malignant tumor patients is higher compared to control groups. We propose that altered Kv1.3 and KCa3.1 expression in CD8⁺ cells in OC could be a reporter and may serve as a biomarker in diagnostics and that increased Ca²⁺ response through CRAC may contribute to the impaired CD8⁺ function.

Ion channels of T cells (Kv1.3, KCa3.1, and CRAC) participate in the regulation of activation and effector functions via modulation of the Ca²⁺-dependent pathway. T cells expressing chimeric antigen receptors (CAR T cells) showed a remarkable role in anti-tumor therapy, especially in the treatment of chemotherapy-resistant liquid cancers. Nevertheless, many challenges remain to be overcome to improve the treatment for solid tumors. In this study, we assessed the expression and role of ion channels in CAR T cells. We found that HER2-specific CAR T cells had higher KCa3.1 conductance compared to the non-transduced (NT, control) cells, which was more prominent in the CD8⁺ population (CD4⁺ cell also showed elevation). Conversely, the Kv1.3 expression level was the same for all cell types (CD4⁺, CD8⁺, CAR, and NT). Single-cell Ca²⁺ imaging revealed that thapsigargin-induced SOCE via CRAC is suppressed in CD8⁺ CAR T cells, unlike for CD4⁺ and CD8⁺ NT cells. To dissect the functional role of Kv1.3 and KCa3.1, we used specific antagonists (Kv1.3: Vm24; KCa3.1: TRAM-34): the target cell elimination capacity of the CD8⁺ CAR T cells was improved either by blocking KCa3.1 or Kv1.3. These results imply that ion channels could be a target in CAR T cell immunotherapy elaboration.