转移性结直肠癌患者 TIL（肿瘤浸润淋巴细胞）中钙库操纵性 Ca(2+) 内流上调

(1) Background: Store-operated Ca 2+ entry (SOCE) drives the cytotoxic activity of cytotoxic T lymphocytes (CTLs) against cancer cells.

However, SOCE can be enhanced in cancer cells due to an increase in the expression and/or function of its underlying molecular components, i. e. , STIM1 and Orai1.

Herein, we evaluated the SOCE expression and function in tumour-infiltrating lymphocytes (TILs) from metastatic colorectal cancer (mCRC) patients. (2) Methods: Functional studies were conducted in TILs expanded ex vivo from CRC liver metastases. Peripheral blood T cells from healthy donors (hPBTs) and mCRC patients (cPBTs) were used as controls. (3) Results: SOCE amplitude is enhanced in TILs compared to hPBTs and cPBTs, but the STIM1 protein is only up-regulated in TILs.

Pharmacological manipulation showed that the increase in SOCE mainly depends on tonic modulation by diacylglycerol kinase, which prevents the protein kinase C-dependent inhibition of SOCE activity. The larger SOCE caused a stronger Ca 2+ response to T-cell receptor stimulation by autologous mCRC cells.

Reducing Ca 2+ influx with BTP-2 during target cell killing significantly increases cytotoxic activity at low target:effector ratios. (4) Conclusions: SOCE is enhanced in ex vivo-expanded TILs deriving from mCRC patients but decreasing Ca 2+ influx with BTP-2 increases cytotoxic activity at a low TIL density.