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IL-2 complex recovers steroid-induced inhibition in immunochemotherapy for head and neck cancer
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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819385/ https://www.ncbi.nlm.nih.gov/pubmed/35123188 http://dx.doi.org/10.1016/j.tranon.2022.101358 |
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author | Kono, Michihisa Yamaki, Hidekiyo Komatsuda, Hiroki Kumai, Takumi Hayashi, Ryusuke Wakisaka, Risa Sato, Ryosuke Ohara, Kenzo Kishibe, Kan Takahara, Miki Katada, Akihiro Hayashi, Tatsuya Harabuchi, Yasuaki |
author_facet | Kono, Michihisa Yamaki, Hidekiyo Komatsuda, Hiroki Kumai, Takumi Hayashi, Ryusuke Wakisaka, Risa Sato, Ryosuke Ohara, Kenzo Kishibe, Kan Takahara, Miki Katada, Akihiro Hayashi, Tatsuya Harabuchi, Yasuaki |
author_sort | Kono, Michihisa |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8819385 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-88193852022-02-09 IL-2 complex recovers steroid-induced inhibition in immunochemotherapy for head and neck cancer Kono, Michihisa Yamaki, Hidekiyo Komatsuda, Hiroki Kumai, Takumi Hayashi, Ryusuke Wakisaka, Risa Sato, Ryosuke Ohara, Kenzo Kishibe, Kan Takahara, Miki Katada, Akihiro Hayashi, Tatsuya Harabuchi, Yasuaki Transl Oncol Original Research 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. Neoplasia Press 2022-02-02 /pmc/articles/PMC8819385/ /pubmed/35123188 http://dx.doi.org/10.1016/j.tranon.2022.101358 Text en © 2022 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Kono, Michihisa Yamaki, Hidekiyo Komatsuda, Hiroki Kumai, Takumi Hayashi, Ryusuke Wakisaka, Risa Sato, Ryosuke Ohara, Kenzo Kishibe, Kan Takahara, Miki Katada, Akihiro Hayashi, Tatsuya Harabuchi, Yasuaki IL-2 complex recovers steroid-induced inhibition in immunochemotherapy for head and neck cancer |
title | IL-2 complex recovers steroid-induced inhibition in immunochemotherapy for head and neck cancer |
title_full | IL-2 complex recovers steroid-induced inhibition in immunochemotherapy for head and neck cancer |
title_fullStr | IL-2 complex recovers steroid-induced inhibition in immunochemotherapy for head and neck cancer |
title_full_unstemmed | IL-2 complex recovers steroid-induced inhibition in immunochemotherapy for head and neck cancer |
title_short | IL-2 complex recovers steroid-induced inhibition in immunochemotherapy for head and neck cancer |
title_sort | il-2 complex recovers steroid-induced inhibition in immunochemotherapy for head and neck cancer |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819385/ https://www.ncbi.nlm.nih.gov/pubmed/35123188 http://dx.doi.org/10.1016/j.tranon.2022.101358 |
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