STIM1 and STIM2‐mediated Ca2+ influx regulates antitumour immunity by CD8+ T cells

EMBO Molecular Medicine

Carl Weidinger¹  Patrick J. Shaw¹ 

[1] Department of Pathology and Cancer Institute, New York University School of Medicine, New York, NY, USA

关键词: CTL;    SOCE;    STIM1;    STIM2;    tumour immunity;   

DOI  :  10.1002/emmm.201302989

来源: Wiley

【 摘 要 】

Abstract

Store-operated calcium entry (SOCE) through Ca²⁺ release-activated Ca²⁺ (CRAC) channels regulates the function of many immune cells. Patients with loss-of-function mutations in the CRAC channel genes ORAI1 or STIM1 are immunodeficient and are prone to develop virus-associated tumours. This and the reported role of Ca²⁺ signals in cytotoxic lymphocyte function suggest that SOCE may be critical for tumour immune surveillance. Using conditional knock out mice lacking STIM1 and its homologue STIM2, we find that SOCE in CD8⁺ T cells is required to prevent the engraftment of melanoma and colon carcinoma cells and to control tumour growth. SOCE is essential for the cytotoxic function of CTLs both in vivo and in vitro by regulating the degranulation of CTLs, their expression of Fas ligand and production of TNF-α and IFN-γ. Our results emphasize an important role of SOCE in antitumour immunity, which is significant given recent reports arguing in favour of CRAC channel inhibition for cancer therapy.

【 授权许可】

CC BY   
Copyright © 2013 EMBO Molecular Medicine

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.