Open AccessCisplatin‐induced HSF1‐HSP90 axis enhances the expression of functional PD‐L1 in oral squamous cell carcinoma
Author(s) -
Sasaya Takashi,
Kubo Terufumi,
Murata Kenji,
Mizue Yuka,
Sasaki Kenta,
Yanagawa Junko,
Imagawa Makoto,
Kato Hirotaka,
Tsukahara Tomohide,
Kanaseki Takayuki,
Tamura Yasuaki,
Miyazaki Akihiro,
Hirohashi Yoshihiko,
Torigoe Toshihiko
Publication year - 2023
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.5310
Subject(s) - immunotherapy , cancer research , cisplatin , medicine , heat shock protein , immune system , hsf1 , cytotoxic t cell , chemotherapy , cancer , immune checkpoint , immunology , oncology , biology , hsp70 , in vitro , gene , biochemistry
Immune checkpoint inhibitor‐based cancer immunotherapy has provided an additional therapeutic option for oral squamous cell carcinoma (OSCC) with recurrence or distant metastases. However, further improvement of OSCC treatment is required to develop the optimal combination or order for chemoradiotherapy and immunotherapy. Along with the accumulation of clinical knowledge and evidence, it is also essential to clarify the biological impact of chemo‐radiotherapeutic agents on the cancer immune microenvironment. In this study, we investigated the effects of cisplatin (CDDP), a key therapeutic agent for OSCC, on programmed death‐ligand 1 (PD‐L1) expression in OSCC lines. Although CDDP treatment increased the surface levels of PD‐L1 on OSCC cell lines, the gene and total protein expression levels of PD‐L1 were not altered. We also demonstrated that the phosphorylation of heat shock factor 1 and heat shock protein 90 was involved in this process. In addition, CDDP‐induced PD‐L1 attenuated the target‐specific cytotoxic T lymphocyte reaction to OSCC. These results provide an immunobiological basis for the response of OSCC to CDDP and will contribute to our biological understanding of the action of novel combination therapy including immunotherapy together with platinum‐based chemotherapy for OSCC.