Exploiting Ca2+ signaling in T cells to advance cancer immunotherapy.

Abstract

Decades of basic research has established the importance of Ca2+ to various T cell functions, such as cytotoxicity, proliferation, differentiation and cytokine secretion. We now have a good understanding of how proximal TCR signaling initiates Ca2+ influx and how this influx subsequently changes transcriptional activities in T cells. As chimeric antigen receptor (CAR)-T therapy has achieved great clinical success, is it possible to harness Ca2+ signaling to further advance CAR-T research? How is CAR signaling different from TCR signaling? How can functional CARs be identified in a high-throughput way? Quantification of various Ca2+ signals downstream of CAR/TCR activation might help answer these questions. Here we first summarized recent studies that used Ca2+ dye, genetically-encoded Ca2+ indicators (GECI) or transcriptional activity reporters to understand CAR activation in vitro and in vivo. We next reviewed several proof-of-concept reports that manipulate Ca2+ signaling by light or ultrasound to achieve precise spatiotemporal control of T cell functions. These efforts, though preliminary, opened up new avenues to solve the on-target/off-tumor problem of therapeutic T cells. Other modalities to regulate Ca2+ signaling, such as radio wave and electrical pulse, were also discussed. Thus, monitoring or manipulating Ca2+ signaling in T cells provides us many opportunities to advance cancer immunotherapy.

• Authors: Xianhui Meng, Xiaoyan Wu, Yuyuan Zheng, Kai Shang, Ruirui Jing, Peng Jiao, Chun Zhou, Jing Zhou, Jie Sun
• Journal: Seminars in immunology (Semin Immunol) Vol. 49 Pg. 101434 (06 2020) ISSN: 1096-3618 [Electronic] England
• PMID: 33272900 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Receptors, Antigen, T-Cell
• Receptors, Chimeric Antigen
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Calcium Signaling
• Humans
• Immunotherapy (adverse effects, methods)
• Immunotherapy, Adoptive
• Neoplasms (immunology, metabolism, pathology, therapy)
• Receptors, Antigen, T-Cell (metabolism)
• Receptors, Chimeric Antigen
• Signal Transduction
• T-Lymphocytes (immunology, metabolism)