دورية أكاديمية
MHC-I upregulation safeguards neoplastic T cells in the skin against NK cell-mediated eradication in mycosis fungoides
| العنوان: | MHC-I upregulation safeguards neoplastic T cells in the skin against NK cell-mediated eradication in mycosis fungoides |
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| المؤلفون: | Chang, Yun-Tsan, Prompsy, Pacôme, Kimeswenger, Susanne, Tsai, Yi-Chien, Ignatova, Desislava, Pavlova, Olesya, Iselin, Christoph, French, Lars E., Levesque, Mitchell P., Kuonen, François, Bobrowicz, Malgorzata, Brunner, Patrick M., Pascolo, Steve, Hoetzenecker, Wolfram, Guenova, Emmanuella |
| المساهمون: | Promedica Stiftung, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Université de Lausanne |
| المصدر: | Nature Communications ; volume 15, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | Cancer-associated immune dysfunction is a major challenge for effective therapies. The emergence of antibodies targeting tumor cell-surface antigens led to advancements in the treatment of hematopoietic malignancies, particularly blood cancers. Yet their impact is constrained against tumors of hematopoietic origin manifesting in the skin. In this study, we employ a clonality-supervised deep learning methodology to dissect key pathological features implicated in mycosis fungoides, the most common cutaneous T-cell lymphoma. Our investigations unveil the prominence of the IL-32β–major histocompatibility complex (MHC)-I axis as a critical determinant in tumor T-cell immune evasion within the skin microenvironment. In patients’ skin, we find MHC-I to detrimentally impact the functionality of natural killer (NK) cells, diminishing antibody-dependent cellular cytotoxicity and promoting resistance of tumor skin T-cells to cell-surface targeting therapies. Through murine experiments in female mice, we demonstrate that disruption of the MHC-I interaction with NK cell inhibitory Ly49 receptors restores NK cell anti-tumor activity and targeted T-cell lymphoma elimination in vivo. These findings underscore the significance of attenuating the MHC-I-dependent immunosuppressive networks within skin tumors. Overall, our study introduces a strategy to reinvigorate NK cell-mediated anti-tumor responses to overcome treatment resistance to existing cell-surface targeted therapies for skin lymphoma. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-024-45083-8 |
| الإتاحة: | https://doi.org/10.1038/s41467-024-45083-8Test https://www.nature.com/articles/s41467-024-45083-8.pdfTest https://www.nature.com/articles/s41467-024-45083-8Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.8746A43C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-024-45083-8 |
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