HLA class II neoantigen presentation for CD4+ T cell surveillance in HLA class II-negative colorectal cancer
Neoantigen-reactive CD4+ T cells play a key role in the anti-tumor immune response. However, the majority of epithelial tumors are negative for HLA class II (HLA-II) surface expression, and less is known about the processing of HLA-II antigens. Here, we directly identified naturally presented HLA-II...
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| Format: | Article |
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Taylor & Francis Group
2024-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2404665 |
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| author | Satoru Matsumoto Takahiro Tsujikawa Serina Tokita Mai Mohamed Bedeir Kazuhiko Matsuo Fumitake Hata Yoshihiko Hirohashi Takayuki Kanaseki Toshihiko Torigoe |
| author_facet | Satoru Matsumoto Takahiro Tsujikawa Serina Tokita Mai Mohamed Bedeir Kazuhiko Matsuo Fumitake Hata Yoshihiko Hirohashi Takayuki Kanaseki Toshihiko Torigoe |
| author_sort | Satoru Matsumoto |
| collection | DOAJ |
| description | Neoantigen-reactive CD4+ T cells play a key role in the anti-tumor immune response. However, the majority of epithelial tumors are negative for HLA class II (HLA-II) surface expression, and less is known about the processing of HLA-II antigens. Here, we directly identified naturally presented HLA-II neoantigens in HLA-II negative colorectal cancer (CRC) tissue using a proteogenomic approach. The neoantigens were immunogenic and induced patient CD4+ T cells with a Th1-like memory phenotype that produced IFN-γ, IL2 and TNF-α. Multiplex immunohistochemistry (IHC) demonstrated an interaction between Th cells and HLA-II-positive antigen-presenting cells (APCs) at the invasive margin and within the tertiary lymphoid structures (TLS). In our CRC cohort, the density of stromal APCs was associated with HLA-II antigen presentation in the tumor microenvironment (TME), and the number of TLS was positively correlated with the number of somatic mutations in the tumors. These results demonstrate the presence of neoantigen-specific CD4+ surveillance in HLA-II-negative CRC and suggest a potential role for macrophages and dendritic cells (DCs) at the invasive margin and in TLS for antigen presentation. Stromal APCs in the TME can potentially be used as a source for HLA-II neoantigen identification. |
| format | Article |
| id | doaj-art-48ffcd9f1ce14d8b88fdb93819995a7b |
| institution | OA Journals |
| issn | 2162-402X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-48ffcd9f1ce14d8b88fdb93819995a7b2025-08-20T02:38:26ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2024.2404665HLA class II neoantigen presentation for CD4+ T cell surveillance in HLA class II-negative colorectal cancerSatoru Matsumoto0Takahiro Tsujikawa1Serina Tokita2Mai Mohamed Bedeir3Kazuhiko Matsuo4Fumitake Hata5Yoshihiko Hirohashi6Takayuki Kanaseki7Toshihiko Torigoe8Department of Pathology, Sapporo Medical University, Sapporo, JapanDepartment of Otolaryngology–Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, JapanDepartment of Pathology, Sapporo Medical University, Sapporo, JapanDepartment of Otolaryngology–Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, JapanSapporo Clinical Laboratory, Sapporo, JapanDepartment of Surgery, Sapporo Dohto Hospital, Sapporo, JapanDepartment of Pathology, Sapporo Medical University, Sapporo, JapanDepartment of Pathology, Sapporo Medical University, Sapporo, JapanDepartment of Pathology, Sapporo Medical University, Sapporo, JapanNeoantigen-reactive CD4+ T cells play a key role in the anti-tumor immune response. However, the majority of epithelial tumors are negative for HLA class II (HLA-II) surface expression, and less is known about the processing of HLA-II antigens. Here, we directly identified naturally presented HLA-II neoantigens in HLA-II negative colorectal cancer (CRC) tissue using a proteogenomic approach. The neoantigens were immunogenic and induced patient CD4+ T cells with a Th1-like memory phenotype that produced IFN-γ, IL2 and TNF-α. Multiplex immunohistochemistry (IHC) demonstrated an interaction between Th cells and HLA-II-positive antigen-presenting cells (APCs) at the invasive margin and within the tertiary lymphoid structures (TLS). In our CRC cohort, the density of stromal APCs was associated with HLA-II antigen presentation in the tumor microenvironment (TME), and the number of TLS was positively correlated with the number of somatic mutations in the tumors. These results demonstrate the presence of neoantigen-specific CD4+ surveillance in HLA-II-negative CRC and suggest a potential role for macrophages and dendritic cells (DCs) at the invasive margin and in TLS for antigen presentation. Stromal APCs in the TME can potentially be used as a source for HLA-II neoantigen identification.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2404665Antigen presentationHLA class IIneoantigentertiary lymphoid structuresTh1 cells |
| spellingShingle | Satoru Matsumoto Takahiro Tsujikawa Serina Tokita Mai Mohamed Bedeir Kazuhiko Matsuo Fumitake Hata Yoshihiko Hirohashi Takayuki Kanaseki Toshihiko Torigoe HLA class II neoantigen presentation for CD4+ T cell surveillance in HLA class II-negative colorectal cancer OncoImmunology Antigen presentation HLA class II neoantigen tertiary lymphoid structures Th1 cells |
| title | HLA class II neoantigen presentation for CD4+ T cell surveillance in HLA class II-negative colorectal cancer |
| title_full | HLA class II neoantigen presentation for CD4+ T cell surveillance in HLA class II-negative colorectal cancer |
| title_fullStr | HLA class II neoantigen presentation for CD4+ T cell surveillance in HLA class II-negative colorectal cancer |
| title_full_unstemmed | HLA class II neoantigen presentation for CD4+ T cell surveillance in HLA class II-negative colorectal cancer |
| title_short | HLA class II neoantigen presentation for CD4+ T cell surveillance in HLA class II-negative colorectal cancer |
| title_sort | hla class ii neoantigen presentation for cd4 t cell surveillance in hla class ii negative colorectal cancer |
| topic | Antigen presentation HLA class II neoantigen tertiary lymphoid structures Th1 cells |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2404665 |
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