Stratification of the immunotypes of tongue squamous cell carcinoma to improve prognosis and the response to immune checkpoint inhibitors
Abstract Objectives An understanding of the tumor immune microenvironment is required to improve treatment, especially the selection of immune checkpoint inhibitors (ICIs). In this study, we stratified the immunotypes of tongue squamous cell carcinoma (TSCC) based on the results of comprehensive imm...
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Springer
2025-03-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-025-03982-9 |
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| author | Yuya Su Ryo Ouchi Pissacha Daroonpan Miwako Hamagaki Tohru Ikeda Noji Rika Naoto Nishii Fumihiko Tsushima Yoshihito Kano Takahiro Asakage Makoto Noguchi Hiroyuki Harada Miyuki Azuma |
| author_facet | Yuya Su Ryo Ouchi Pissacha Daroonpan Miwako Hamagaki Tohru Ikeda Noji Rika Naoto Nishii Fumihiko Tsushima Yoshihito Kano Takahiro Asakage Makoto Noguchi Hiroyuki Harada Miyuki Azuma |
| author_sort | Yuya Su |
| collection | DOAJ |
| description | Abstract Objectives An understanding of the tumor immune microenvironment is required to improve treatment, especially the selection of immune checkpoint inhibitors (ICIs). In this study, we stratified the immunotypes of tongue squamous cell carcinoma (TSCC) based on the results of comprehensive immune profiling. Methods We enrolled 87 therapy-naïve TSCC and 17 ICI-treated TSCC patients who underwent glossectomy without any other prior therapy. Comprehensive immune profile analyses employed multiplex immunofluorescence and tissue imaging. Results Based on the hierarchies of 58 immune parameters and the spatial distances between cytotoxic T lymphocytes (CTL) and tumor cells, we stratified five immunotypes: Immunoactive type I, border type II, immunosuppressed type III, immunoisolating type IV, and immunodesert type V. The type I frequency was only 16%. Most TSCCs (~ 70%) were of types III–V. The CTL density (CTL-D) was closely correlated with the PD-L1+ pan-macrophages (panM)-D, and the panM-D closely correlated with the PD-1+ CTL-D. This indicated that PD-1 and PD-L1 expression required macrophages and CTL recruitment in the tumor microenvironment. No ICI-treated TSCC patients, all of whom were recurrent/metastatic cases, were of the type I immunotype, and almost half (47.0%) were of the immunodesert type V. Most cases exhibited an imbalance between T-cell PD-1 and macrophage PD-L1 expression. Conclusion We defined five TSCC-specific immunotypes based on the results of comprehensive immune profiling analyses. Immunoactive type, which would be sensitive to ICI monotherapy, was rare, and most TSCC cases exhibited immune-regulated immunotypes. Immunotype-based personalized treatments are required to improve clinical outcomes. |
| format | Article |
| id | doaj-art-0752fe66d0e142cda86b1c117f82638d |
| institution | DOAJ |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-0752fe66d0e142cda86b1c117f82638d2025-08-20T02:49:23ZengSpringerCancer Immunology, Immunotherapy1432-08512025-03-0174411410.1007/s00262-025-03982-9Stratification of the immunotypes of tongue squamous cell carcinoma to improve prognosis and the response to immune checkpoint inhibitorsYuya Su0Ryo Ouchi1Pissacha Daroonpan2Miwako Hamagaki3Tohru Ikeda4Noji Rika5Naoto Nishii6Fumihiko Tsushima7Yoshihito Kano8Takahiro Asakage9Makoto Noguchi10Hiroyuki Harada11Miyuki Azuma12Department of Oral and Maxillofacial Surgical Oncology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO)Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU)Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU)Division of Surgical Pathology, Institute of Science Tokyo HospitalDepartment of Oral Pathology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO)Department of Oral and Maxillofacial Surgical Oncology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO)Department of Oral and Maxillofacial Surgical Oncology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO)Department of Oral and Maxillofacial Surgical Oncology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO)Department of Medical Oncology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO)Department of Head and Neck Surgery, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO)Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of ToyamaDepartment of Oral and Maxillofacial Surgical Oncology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO)Department of Oral and Maxillofacial Surgical Oncology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO)Abstract Objectives An understanding of the tumor immune microenvironment is required to improve treatment, especially the selection of immune checkpoint inhibitors (ICIs). In this study, we stratified the immunotypes of tongue squamous cell carcinoma (TSCC) based on the results of comprehensive immune profiling. Methods We enrolled 87 therapy-naïve TSCC and 17 ICI-treated TSCC patients who underwent glossectomy without any other prior therapy. Comprehensive immune profile analyses employed multiplex immunofluorescence and tissue imaging. Results Based on the hierarchies of 58 immune parameters and the spatial distances between cytotoxic T lymphocytes (CTL) and tumor cells, we stratified five immunotypes: Immunoactive type I, border type II, immunosuppressed type III, immunoisolating type IV, and immunodesert type V. The type I frequency was only 16%. Most TSCCs (~ 70%) were of types III–V. The CTL density (CTL-D) was closely correlated with the PD-L1+ pan-macrophages (panM)-D, and the panM-D closely correlated with the PD-1+ CTL-D. This indicated that PD-1 and PD-L1 expression required macrophages and CTL recruitment in the tumor microenvironment. No ICI-treated TSCC patients, all of whom were recurrent/metastatic cases, were of the type I immunotype, and almost half (47.0%) were of the immunodesert type V. Most cases exhibited an imbalance between T-cell PD-1 and macrophage PD-L1 expression. Conclusion We defined five TSCC-specific immunotypes based on the results of comprehensive immune profiling analyses. Immunoactive type, which would be sensitive to ICI monotherapy, was rare, and most TSCC cases exhibited immune-regulated immunotypes. Immunotype-based personalized treatments are required to improve clinical outcomes.https://doi.org/10.1007/s00262-025-03982-9Oral cancerImmune checkpoint inhibitorImmunotherapyImmunotypesTumor microenvironment |
| spellingShingle | Yuya Su Ryo Ouchi Pissacha Daroonpan Miwako Hamagaki Tohru Ikeda Noji Rika Naoto Nishii Fumihiko Tsushima Yoshihito Kano Takahiro Asakage Makoto Noguchi Hiroyuki Harada Miyuki Azuma Stratification of the immunotypes of tongue squamous cell carcinoma to improve prognosis and the response to immune checkpoint inhibitors Cancer Immunology, Immunotherapy Oral cancer Immune checkpoint inhibitor Immunotherapy Immunotypes Tumor microenvironment |
| title | Stratification of the immunotypes of tongue squamous cell carcinoma to improve prognosis and the response to immune checkpoint inhibitors |
| title_full | Stratification of the immunotypes of tongue squamous cell carcinoma to improve prognosis and the response to immune checkpoint inhibitors |
| title_fullStr | Stratification of the immunotypes of tongue squamous cell carcinoma to improve prognosis and the response to immune checkpoint inhibitors |
| title_full_unstemmed | Stratification of the immunotypes of tongue squamous cell carcinoma to improve prognosis and the response to immune checkpoint inhibitors |
| title_short | Stratification of the immunotypes of tongue squamous cell carcinoma to improve prognosis and the response to immune checkpoint inhibitors |
| title_sort | stratification of the immunotypes of tongue squamous cell carcinoma to improve prognosis and the response to immune checkpoint inhibitors |
| topic | Oral cancer Immune checkpoint inhibitor Immunotherapy Immunotypes Tumor microenvironment |
| url | https://doi.org/10.1007/s00262-025-03982-9 |
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