| Autor: |
Michihisa Kono, Hidekiyo Yamaki, Hiroki Komatsuda, Takumi Kumai, Ryusuke Hayashi, Risa Wakisaka, Ryosuke Sato, Kenzo Ohara, Kan Kishibe, Miki Takahara, Akihiro Katada, Tatsuya Hayashi, Yasuaki Harabuchi |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Translational Oncology, Vol 18, Iss , Pp 101358- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1936-5233 |
| DOI: |
10.1016/j.tranon.2022.101358 |
| Popis: |
Background: A combination therapy with immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy has become the first-line treatment for recurrent or metastatic head and neck squamous carcinoma (HNSCC). Although steroids are often used as anti-emetic medications during chemotherapy, their adverse effects on immune-combined chemotherapy are unclear in HNSCC.Methods: The effects of dexamethasone on tumor growth and immune cell population were evaluated in a mouse HNSCC model treated with PD-1 blockade combined with cisplatin. The effect of various doses of dexamethasone on cell proliferation, survival, surface markers, IFN-γ production, and antitumor effects in antigen-specific T cells was examined in vitro. The recovery of T cell dysfunction by IL-2 was assessed in vitro and in vivo.Results: In a mouse HNSCC model, dexamethasone showed limited antitumor effects on immunochemotherapy. Dexamethasone decreased the number of T cells and inhibited T cell differentiation into effector and central memory T cells. In the in vitro assessment, dexamethasone induced cell death, limited proliferation, and reduced the reactivity against HNSCC cell lines of antigen-specific T cells in a dose-dependent manner. The expression of inhibitory receptors on T cells was not affected by steroids. This inhibition was recovered by IL-2 and IL-2/anti-IL-2 complexes (IL-2 Cx) in vitro and in vivo, respectively.Conclusion: Our preclinical data indicate that dexamethasone diminishes the antitumor effects of immunochemotherapy in patients with HNSCC. IL-2 Cx recovered the inhibition of antitumor immunity by steroids and might be a potent immune adjuvant for patients who require steroids during PD-1 blockade and chemotherapy. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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