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Immune‐checkpoint molecules on regulatory T‐cells as a potential therapeutic target in head and neck squamous cell cancers

Immune‐checkpoint inhibitors improve the survival of head and neck squamous cell carcinoma (HNSCC) patients. Although recent studies have demonstrated that the tumor immune microenvironment (TIME) has critical roles in immunotherapy, the precise mechanisms involved are unclear. Therefore, further in...

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Autores principales: Suzuki, Susumu, Ogawa, Tetsuya, Sano, Rui, Takahara, Taishi, Inukai, Daisuke, Akira, Satou, Tsuchida, Hiromi, Yoshikawa, Kazuhiro, Ueda, Ryuzo, Tsuzuki, Toyonori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293074/
https://www.ncbi.nlm.nih.gov/pubmed/32304268
http://dx.doi.org/10.1111/cas.14422
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author Suzuki, Susumu
Ogawa, Tetsuya
Sano, Rui
Takahara, Taishi
Inukai, Daisuke
Akira, Satou
Tsuchida, Hiromi
Yoshikawa, Kazuhiro
Ueda, Ryuzo
Tsuzuki, Toyonori
author_facet Suzuki, Susumu
Ogawa, Tetsuya
Sano, Rui
Takahara, Taishi
Inukai, Daisuke
Akira, Satou
Tsuchida, Hiromi
Yoshikawa, Kazuhiro
Ueda, Ryuzo
Tsuzuki, Toyonori
author_sort Suzuki, Susumu
collection PubMed
description Immune‐checkpoint inhibitors improve the survival of head and neck squamous cell carcinoma (HNSCC) patients. Although recent studies have demonstrated that the tumor immune microenvironment (TIME) has critical roles in immunotherapy, the precise mechanisms involved are unclear. Therefore, further investigations of TIME are required for the improvement of immunotherapy. The frequency of effector regulatory T‐cells (eTregs) and the expression of immune‐checkpoint molecules (ICM) on eTregs and conventional T‐cells (Tconvs) both in peripheral blood lymphocytes (PBL) and tumor‐infiltrating lymphocytes (TIL) from HNSCC patients were analyzed by flow cytometry and their distributions were evaluated by multi‐color immunofluorescence microscopy. High frequency eTreg infiltration into HNSCC tissues was observed and high expressions of CD25, FOXP3, stimulatory‐ICM (4‐1BB, ICOS, OX40 and GITR) and inhibitory‐ICM (programmed cell death‐1 [PD‐1] and cytotoxic T‐lymphocyte‐associated protein‐4 [CTLA‐4]) were found on invasive eTregs. In contrast, the expression of stimulatory‐ICM on Tconvs was low and the expression of inhibitory‐ICM was high. In addition, ICM‐ligands (programmed cell death‐1 [PD‐L1], galectin‐9 and CEACAM‐1) were frequently expressed on cancer cells. PD‐L1 and galectin‐9 were also expressed on macrophages. PD‐1(+) T‐cells interacted with PD‐L1(+) cancer cells or PD‐L1(+) macrophages. This suggested that in TIL, eTregs are highly activated, but Tconvs are exhausted or inactivated by eTregs and immune‐checkpoint systems, and ICM and eTregs are strongly involved in the creation of an immunosuppressive environment in HNSCC tissues. These suggested eTreg targeting drugs are expected to be a combination partner with immune‐checkpoint inhibitors that will improve immunotherapy of HNSCC.
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spelling pubmed-72930742020-06-15 Immune‐checkpoint molecules on regulatory T‐cells as a potential therapeutic target in head and neck squamous cell cancers Suzuki, Susumu Ogawa, Tetsuya Sano, Rui Takahara, Taishi Inukai, Daisuke Akira, Satou Tsuchida, Hiromi Yoshikawa, Kazuhiro Ueda, Ryuzo Tsuzuki, Toyonori Cancer Sci Original Articles Immune‐checkpoint inhibitors improve the survival of head and neck squamous cell carcinoma (HNSCC) patients. Although recent studies have demonstrated that the tumor immune microenvironment (TIME) has critical roles in immunotherapy, the precise mechanisms involved are unclear. Therefore, further investigations of TIME are required for the improvement of immunotherapy. The frequency of effector regulatory T‐cells (eTregs) and the expression of immune‐checkpoint molecules (ICM) on eTregs and conventional T‐cells (Tconvs) both in peripheral blood lymphocytes (PBL) and tumor‐infiltrating lymphocytes (TIL) from HNSCC patients were analyzed by flow cytometry and their distributions were evaluated by multi‐color immunofluorescence microscopy. High frequency eTreg infiltration into HNSCC tissues was observed and high expressions of CD25, FOXP3, stimulatory‐ICM (4‐1BB, ICOS, OX40 and GITR) and inhibitory‐ICM (programmed cell death‐1 [PD‐1] and cytotoxic T‐lymphocyte‐associated protein‐4 [CTLA‐4]) were found on invasive eTregs. In contrast, the expression of stimulatory‐ICM on Tconvs was low and the expression of inhibitory‐ICM was high. In addition, ICM‐ligands (programmed cell death‐1 [PD‐L1], galectin‐9 and CEACAM‐1) were frequently expressed on cancer cells. PD‐L1 and galectin‐9 were also expressed on macrophages. PD‐1(+) T‐cells interacted with PD‐L1(+) cancer cells or PD‐L1(+) macrophages. This suggested that in TIL, eTregs are highly activated, but Tconvs are exhausted or inactivated by eTregs and immune‐checkpoint systems, and ICM and eTregs are strongly involved in the creation of an immunosuppressive environment in HNSCC tissues. These suggested eTreg targeting drugs are expected to be a combination partner with immune‐checkpoint inhibitors that will improve immunotherapy of HNSCC. John Wiley and Sons Inc. 2020-05-19 2020-06 /pmc/articles/PMC7293074/ /pubmed/32304268 http://dx.doi.org/10.1111/cas.14422 Text en © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Suzuki, Susumu
Ogawa, Tetsuya
Sano, Rui
Takahara, Taishi
Inukai, Daisuke
Akira, Satou
Tsuchida, Hiromi
Yoshikawa, Kazuhiro
Ueda, Ryuzo
Tsuzuki, Toyonori
Immune‐checkpoint molecules on regulatory T‐cells as a potential therapeutic target in head and neck squamous cell cancers
title Immune‐checkpoint molecules on regulatory T‐cells as a potential therapeutic target in head and neck squamous cell cancers
title_full Immune‐checkpoint molecules on regulatory T‐cells as a potential therapeutic target in head and neck squamous cell cancers
title_fullStr Immune‐checkpoint molecules on regulatory T‐cells as a potential therapeutic target in head and neck squamous cell cancers
title_full_unstemmed Immune‐checkpoint molecules on regulatory T‐cells as a potential therapeutic target in head and neck squamous cell cancers
title_short Immune‐checkpoint molecules on regulatory T‐cells as a potential therapeutic target in head and neck squamous cell cancers
title_sort immune‐checkpoint molecules on regulatory t‐cells as a potential therapeutic target in head and neck squamous cell cancers
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293074/
https://www.ncbi.nlm.nih.gov/pubmed/32304268
http://dx.doi.org/10.1111/cas.14422
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