Sion of intercellular adhesion molecule-1 and enhances natural killer cell sensitivity on L-type calcium channel

December 28, 2022

Sion of intercellular adhesion molecule-1 and enhances natural killer cell sensitivity on L-type calcium channel Compound cancer cellsSimin Li, Tomoyuki Nishikawa and Yasufumi KanedaDivision of Gene Therapy Science, Graduate College of Medicine, Osaka University, Osaka, JapanKey words Breast cancer, HVJ-E, ICAM-1, NK, Sendai virus Correspondence Yasufumi Kaneda, Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. Tel: +81-6-6879-3901; Fax: +81-6-6879-3909; E-mail: [email protected] Funding Information Promotion of Fundamental Studies in Wellness Sciences with the National Institute of Biomedical Innovation (Project ID: 10-03) and Grant-in-Aid for Scientific Investigation (B) from Japan Society for the Promotion of Science. Received April 13, 2017; Revised September 17, 2017; Accepted September 21, 2017 Cancer Sci 108 (2017) 2333341 doi: 10.1111/cas.We’ve currently reported that the inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) has various anticancer effects, including induction of cancer-selective cell death and activation of anticancer immunity. The HVJ-E stimulates dendritic cells to produce cytokines and chemokines which include b-interferon, interleukin-6, chemokine (C-C motif) ligand 5, and chemokine (C-X-C motif) ligand ten, which activate each CD8+ T cells and natural killer (NK) cells and recruit them for the tumor microenvironment. Having said that, the effect of HVJ-E on modulating the sensitivity of cancer cells to immune cell attack has but to become investigated. In this study, we found that HVJ-E induced the production of intercellular adhesion molecule-1 (ICAM-1, CD54), a ligand of lymphocyte functionassociated antigen 1, in various cancer cell lines through the activation of nuclear factor-jB downstream of retinoic acid-inducible gene I as well as the mitochondrial antiviral signaling pathway. The upregulation of ICAM-1 around the surface of cancer cells increased the sensitivity of cancer cells to NK cells. Knocking out expression of ICAM-1 in MDA-MB-231 cells utilizing the CRISPR/Cas9 strategy significantly decreased the killing effect of NK cells on ICAM-1-depleted MDA-MB-231 cells. Furthermore, HVJ-E suppressed tumor development in MDA-MB-231 tumor-bearing SCID mice, and also the HVJ-E antitumor impact was impaired when NK cells were depleted by remedy using the anti-asialo GM1 antibody. Our findings recommend that HVJ-E enhances NK cell sensitivity against cancer cells by growing ICAM-1 expression on the cancer cell surface.Cancer is really a top cause of death worldwide, and its prevalence is escalating because of aging and lifestyle alterations.(1,2) Presently, you can find lots of sorts of cancer therapy, including surgery, targeted therapy, chemotherapy, radiotherapy, and immunotherapy. Lately, the concept of immune-checkpoint inhibition has given rise to breakthroughs in cancer immunotherapy. Antibodies against immune-checkpoint molecules for example PD-1, PD-L1, and CTL linked protein-4 activate CTL against cancers by stopping the inhibitory signal of CD8+ T cells.(three) Although antibodies against PD-1 and PDL1 resulted in remission in 5-HT Receptor custom synthesis malignant melanoma, approximately 70 of patients are still resistant to these antibody treatments.(7) The insensitivity to immune-checkpoint inhibitory therapies is usually a big concern in cancer remedy worldwide. Active b-catenin signaling in melanoma prevents chemokine CCL4 production, which benefits in the inhibition of dendritic cell infiltration and su.