Tumor-infiltrating B cells produce tumor-specific antibodies and may contribute to suppressing tumor in head and neck squamous cell carcinoma
The involvement of T cells, particularly cytotoxic T cells, in tumor immunity has been reported, but the roles of B cells and antibodies in tumor immunity remain unclear. Previous studies have primarily focused on circulating B cells in the blood, with limited investigation of tumor-infiltrating B c...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2543019 |
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| author | Junsei Sameshima Hu Chen Naoki Kaneko Lijing Yan Shiho Yokomizo Tomoki Sueyoshi Haruki Nagano Taiki Sakamoto Shoichi Tanaka Yasuyuki Maruse Taichi Hattori Ryoji Kitamura Yoshikazu Hayashi Takashi Maehara Shinsuke Fujii Tamotsu Kiyoshima Thomas Guy Zivile Giedraityte Wataru Kumamaru Masafumi Moriyama Shintaro Kawano |
| author_facet | Junsei Sameshima Hu Chen Naoki Kaneko Lijing Yan Shiho Yokomizo Tomoki Sueyoshi Haruki Nagano Taiki Sakamoto Shoichi Tanaka Yasuyuki Maruse Taichi Hattori Ryoji Kitamura Yoshikazu Hayashi Takashi Maehara Shinsuke Fujii Tamotsu Kiyoshima Thomas Guy Zivile Giedraityte Wataru Kumamaru Masafumi Moriyama Shintaro Kawano |
| author_sort | Junsei Sameshima |
| collection | DOAJ |
| description | The involvement of T cells, particularly cytotoxic T cells, in tumor immunity has been reported, but the roles of B cells and antibodies in tumor immunity remain unclear. Previous studies have primarily focused on circulating B cells in the blood, with limited investigation of tumor-infiltrating B cells (TIL-Bs) and their secreted antibodies in head and neck squamous cell carcinoma (HNSCC) tissue. This study aimed to clarify TIL-Bs’ role in HNSCC through comprehensive analyses including single-cell RNA sequencing of 68 cases, B-cell receptor repertoire analysis, multiplex immunofluorescence staining, and spatial transcriptomics analysis of resected HNSCC specimens. We identified CXCL13+CD4+ T cells that attract B cells, along with TIL-Bs at various differentiation stages, showing clonal expansion of antibody-secreting cells (ASCs). These ASCs exhibited a low somatic hypermutation frequency, indicating that they are likely activated through extrafollicular response rather than germinal center response. Protein microarrays with recombinant antibodies mimicking TIL-Bs secretory antibodies and serum antibodies revealed several antigens highly expressed in tumor cells. These antigens demonstrated higher expression in tumor cells than normal epithelial cells in the resected HNSCC specimens. Tissue analysis indicated that antibodies binding to these antigens are recognized by macrophage and NK cells with Fc receptors, potentially enhancing tumor immunity. The existence of tumor-infiltrating ASCs showed correlation with favorable prognosis. This study demonstrated for the first time that expanded TIL-Bs produce antibodies and likely contribute to tumor elimination by activating tumor immunity in HNSCC tissues. This novel insight could lead to radically new therapies targeting B cells. |
| format | Article |
| id | doaj-art-07b28b8a3938413397a0f4d5faeec476 |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-07b28b8a3938413397a0f4d5faeec4762025-08-20T03:40:21ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2543019Tumor-infiltrating B cells produce tumor-specific antibodies and may contribute to suppressing tumor in head and neck squamous cell carcinomaJunsei Sameshima0Hu Chen1Naoki Kaneko2Lijing Yan3Shiho Yokomizo4Tomoki Sueyoshi5Haruki Nagano6Taiki Sakamoto7Shoichi Tanaka8Yasuyuki Maruse9Taichi Hattori10Ryoji Kitamura11Yoshikazu Hayashi12Takashi Maehara13Shinsuke Fujii14Tamotsu Kiyoshima15Thomas Guy16Zivile Giedraityte17Wataru Kumamaru18Masafumi Moriyama19Shintaro Kawano20Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanSection of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanSection of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanOBT Research Center, Faculty of Dental Science, Kyushu University, Fukuoka, JapanSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanLaboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanLaboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanRagon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USAFaculty of Medicine, University of Helsinki, Helsinki, FinlandSection of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanSection of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanThe involvement of T cells, particularly cytotoxic T cells, in tumor immunity has been reported, but the roles of B cells and antibodies in tumor immunity remain unclear. Previous studies have primarily focused on circulating B cells in the blood, with limited investigation of tumor-infiltrating B cells (TIL-Bs) and their secreted antibodies in head and neck squamous cell carcinoma (HNSCC) tissue. This study aimed to clarify TIL-Bs’ role in HNSCC through comprehensive analyses including single-cell RNA sequencing of 68 cases, B-cell receptor repertoire analysis, multiplex immunofluorescence staining, and spatial transcriptomics analysis of resected HNSCC specimens. We identified CXCL13+CD4+ T cells that attract B cells, along with TIL-Bs at various differentiation stages, showing clonal expansion of antibody-secreting cells (ASCs). These ASCs exhibited a low somatic hypermutation frequency, indicating that they are likely activated through extrafollicular response rather than germinal center response. Protein microarrays with recombinant antibodies mimicking TIL-Bs secretory antibodies and serum antibodies revealed several antigens highly expressed in tumor cells. These antigens demonstrated higher expression in tumor cells than normal epithelial cells in the resected HNSCC specimens. Tissue analysis indicated that antibodies binding to these antigens are recognized by macrophage and NK cells with Fc receptors, potentially enhancing tumor immunity. The existence of tumor-infiltrating ASCs showed correlation with favorable prognosis. This study demonstrated for the first time that expanded TIL-Bs produce antibodies and likely contribute to tumor elimination by activating tumor immunity in HNSCC tissues. This novel insight could lead to radically new therapies targeting B cells.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2543019Antibodyhead and neck squamous cell carcinomatumor immunityTumor-infiltrating B cells |
| spellingShingle | Junsei Sameshima Hu Chen Naoki Kaneko Lijing Yan Shiho Yokomizo Tomoki Sueyoshi Haruki Nagano Taiki Sakamoto Shoichi Tanaka Yasuyuki Maruse Taichi Hattori Ryoji Kitamura Yoshikazu Hayashi Takashi Maehara Shinsuke Fujii Tamotsu Kiyoshima Thomas Guy Zivile Giedraityte Wataru Kumamaru Masafumi Moriyama Shintaro Kawano Tumor-infiltrating B cells produce tumor-specific antibodies and may contribute to suppressing tumor in head and neck squamous cell carcinoma OncoImmunology Antibody head and neck squamous cell carcinoma tumor immunity Tumor-infiltrating B cells |
| title | Tumor-infiltrating B cells produce tumor-specific antibodies and may contribute to suppressing tumor in head and neck squamous cell carcinoma |
| title_full | Tumor-infiltrating B cells produce tumor-specific antibodies and may contribute to suppressing tumor in head and neck squamous cell carcinoma |
| title_fullStr | Tumor-infiltrating B cells produce tumor-specific antibodies and may contribute to suppressing tumor in head and neck squamous cell carcinoma |
| title_full_unstemmed | Tumor-infiltrating B cells produce tumor-specific antibodies and may contribute to suppressing tumor in head and neck squamous cell carcinoma |
| title_short | Tumor-infiltrating B cells produce tumor-specific antibodies and may contribute to suppressing tumor in head and neck squamous cell carcinoma |
| title_sort | tumor infiltrating b cells produce tumor specific antibodies and may contribute to suppressing tumor in head and neck squamous cell carcinoma |
| topic | Antibody head and neck squamous cell carcinoma tumor immunity Tumor-infiltrating B cells |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2543019 |
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