CD244 represents a new therapeutic target in head and neck squamous cell carcinoma
Background Developing novel strategies to overcome the immunosuppressive tumor microenvironment is a critically important area of cancer therapy research. Here, we assess the therapeutic potential of CD244 (2B4/signaling lymphocyte activation molecule family 4), an immunoregulatory receptor found on...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2020-05-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/1/e000245.full |
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| author | Laura Conforti Laura Agresta Maria Lehn Kristin Lampe Rachel Cantrell Cassandra Hennies Sara Szabo Trisha Wise-Draper Kasper Hoebe Edith M Janssen |
| author_facet | Laura Conforti Laura Agresta Maria Lehn Kristin Lampe Rachel Cantrell Cassandra Hennies Sara Szabo Trisha Wise-Draper Kasper Hoebe Edith M Janssen |
| author_sort | Laura Conforti |
| collection | DOAJ |
| description | Background Developing novel strategies to overcome the immunosuppressive tumor microenvironment is a critically important area of cancer therapy research. Here, we assess the therapeutic potential of CD244 (2B4/signaling lymphocyte activation molecule family 4), an immunoregulatory receptor found on a variety of immune cells, including exhausted CD8+ T cells, dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs).Methods Using de-identified human tumor and blood samples from patients with head and neck squamous cell carcinoma (HNSCC) and HNSCC models in WT and CD244-/- mice, we assessed the therapeutic potential of CD244 using flow cytometry, RT-PCR, Luminex immunoassays and histopathological analyses.Results Compared with healthy tissues, tumor infiltrating CD8+ T cells from HNSCC patients and a HNSCC mouse model showed significant increased expression of CD244 expression that correlated with PD1 expression. Moreover, CD244 was increased on intratumoral DC and MDSC and high CD244 expression correlated with PD-L1 expression and increased spontaneous expression of immune-suppressive mediators. In addition, CD244 activation inhibited production of proinflammatory cytokines in human DC in vitro. Importantly, CD244-/- mice showed significantly impaired tumor growth of HNSCC and interventional treatment of WT mice with anti-CD244 monoclonal antibody significantly impaired the growth of established HNSCC tumors and increased tumor-infiltrating CD8+ T cells.Conclusions Together these data suggest that CD244 contributes to the overall immune-suppressive environment and therefore has potential as a new immunotherapy target in the treatment of malignancies. |
| format | Article |
| id | doaj-art-399509727da14162bd5e3fe439ed4134 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-399509727da14162bd5e3fe439ed41342025-08-20T02:14:28ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-05-018110.1136/jitc-2019-000245CD244 represents a new therapeutic target in head and neck squamous cell carcinomaLaura Conforti0Laura Agresta1Maria Lehn2Kristin Lampe3Rachel Cantrell4Cassandra Hennies5Sara Szabo6Trisha Wise-Draper7Kasper Hoebe8Edith M Janssen9a laura.conforti@uc.edu1 Cancer and Blood Diseases Institute, Cincinnati Children`s Hospital Medical Center, Cincinnati, Ohio, USAUniversity of Cincinnati, Cincinnati, OH, USA2 Division of Immunobiology, Cincinnati Children`s Hospital Research Foundation, Cincinnati, Ohio, USA2 Division of Immunobiology, Cincinnati Children`s Hospital Research Foundation, Cincinnati, Ohio, USA2 Division of Immunobiology, Cincinnati Children`s Hospital Research Foundation, Cincinnati, Ohio, USA3 Division of Pathology & Laboratory Medicine, Cincinnati Children`s Hospital Medical Center, Cincinnati, Ohio, USAUniversity of Cincinnati, Cincinnati, OH, USA6 Immunology Discovery, Janssen Research and Development Spring House, Spring House, Pennsylvania, USA6 Immunology Discovery, Janssen Research and Development Spring House, Spring House, Pennsylvania, USABackground Developing novel strategies to overcome the immunosuppressive tumor microenvironment is a critically important area of cancer therapy research. Here, we assess the therapeutic potential of CD244 (2B4/signaling lymphocyte activation molecule family 4), an immunoregulatory receptor found on a variety of immune cells, including exhausted CD8+ T cells, dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs).Methods Using de-identified human tumor and blood samples from patients with head and neck squamous cell carcinoma (HNSCC) and HNSCC models in WT and CD244-/- mice, we assessed the therapeutic potential of CD244 using flow cytometry, RT-PCR, Luminex immunoassays and histopathological analyses.Results Compared with healthy tissues, tumor infiltrating CD8+ T cells from HNSCC patients and a HNSCC mouse model showed significant increased expression of CD244 expression that correlated with PD1 expression. Moreover, CD244 was increased on intratumoral DC and MDSC and high CD244 expression correlated with PD-L1 expression and increased spontaneous expression of immune-suppressive mediators. In addition, CD244 activation inhibited production of proinflammatory cytokines in human DC in vitro. Importantly, CD244-/- mice showed significantly impaired tumor growth of HNSCC and interventional treatment of WT mice with anti-CD244 monoclonal antibody significantly impaired the growth of established HNSCC tumors and increased tumor-infiltrating CD8+ T cells.Conclusions Together these data suggest that CD244 contributes to the overall immune-suppressive environment and therefore has potential as a new immunotherapy target in the treatment of malignancies.https://jitc.bmj.com/content/8/1/e000245.full |
| spellingShingle | Laura Conforti Laura Agresta Maria Lehn Kristin Lampe Rachel Cantrell Cassandra Hennies Sara Szabo Trisha Wise-Draper Kasper Hoebe Edith M Janssen CD244 represents a new therapeutic target in head and neck squamous cell carcinoma Journal for ImmunoTherapy of Cancer |
| title | CD244 represents a new therapeutic target in head and neck squamous cell carcinoma |
| title_full | CD244 represents a new therapeutic target in head and neck squamous cell carcinoma |
| title_fullStr | CD244 represents a new therapeutic target in head and neck squamous cell carcinoma |
| title_full_unstemmed | CD244 represents a new therapeutic target in head and neck squamous cell carcinoma |
| title_short | CD244 represents a new therapeutic target in head and neck squamous cell carcinoma |
| title_sort | cd244 represents a new therapeutic target in head and neck squamous cell carcinoma |
| url | https://jitc.bmj.com/content/8/1/e000245.full |
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