Internal medicine

Immunotherapy

Nifedipine

Colorectal cancer

Cancer

Immunology

Metastasis

Tumor progression

Calcium channel blocker

Calcium

Immune checkpoint

Cancer research

Medicine

Calcium channel

Immune system

Pharmacology

Cell Reports

Abnormal activation of calcium channels has been shown to play crucial roles in tumor occurrence and development. However, the role of inhibitors targeting calcium channels in tumor progression and immune regulation remains unclear, and their clinical applications are still limited. We show that nifedipine (NIFE), a calcium channel blocker, inhibits calcium influx to impair nuclear factor of activated T cell 2 (NFAT2) dephosphorylation, activation, and nuclear translocation, thus preventing transcriptional activation of downstream signaling molecules to suppress colorectal cancer (CRC) proliferation and metastasis. In addition, NIFE decreases expression of programmed death-ligand 1 (PD-L1) on CRC cells and programmed death-1 (PD-1) on CD8+ T cells and reactivates tumor immune monitoring, which may stimulate or enhance PD-1-based antitumor immunotherapy. Our findings provide direct evidence that NIFE is a promising clinical therapy to treat patients with advanced CRC by affecting the tumor itself and tumor immunity. NIFE may be a promising therapeutic option to enhance effectiveness of immune checkpoint blockade therapy in CRC.

Calcium Channel Blocker Nifedipine Suppresses Colorectal Cancer Progression and Immune Escape by Preventing NFAT2 Nuclear Translocation