Layilin augments integrin activation to promote antitumor immunity
| العنوان: | Layilin augments integrin activation to promote antitumor immunity |
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| المؤلفون: | Pooja Mehta, Jacob M. Luber, Anubhav N. Mathur, James A. Wells, Kelly M. Mahuron, Luv Panjabi, Joshua M. Moreau, Eric Shifrut, Margaret M. Lowe, Meromit Singer, Victoire Gouirand, Mariela L. Pauli, Jeff E. Glasgow, Ray Jupp, Devi P. Boda, Alexander Marson, Robby Grewal, Adil Daud, Michael Alvarado, Michael Rosenblum, Renny M Feldman |
| المصدر: | The Journal of Experimental Medicine The Journal of experimental medicine, vol 217, iss 9 |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Cytotoxicity, Immunologic, Talin, Integrins, Cytotoxicity, CD8-Positive T-Lymphocytes, Inbred C57BL, Lymphocyte Activation, Medical and Health Sciences, Mice, 0302 clinical medicine, Immunologic, Lectins, Neoplasms, Immunology and Allergy, Cytotoxic T cell, 2.1 Biological and endogenous factors, Lymphocyte function-associated antigen 1, Lymphocytes, Aetiology, Neoplasm Metastasis, Melanoma, Cancer, Gene Editing, Membrane Glycoproteins, biology, C-Type, Chemistry, Lymphocyte Function-Associated Antigen-1, Cell biology, 030220 oncology & carcinogenesis, Tumor immunology, Cytokines, Protein Binding, 1.1 Normal biological development and functioning, Integrin, Immunology, Article, 03 medical and health sciences, Immune system, Lymphocytes, Tumor-Infiltrating, Underpinning research, Cell Adhesion, Animals, Humans, Lectins, C-Type, Tumor-Infiltrating, Solid Tumors, Cell adhesion, Cell Proliferation, Cell growth, Immunity, biochemical phenomena, metabolism, and nutrition, Clone Cells, Mice, Inbred C57BL, 030104 developmental biology, Cancer cell, biology.protein, Carrier Proteins, CD8 |
| الوصف: | The C-type lectin layilin has been observed in several human cancers, but its function on immune cells is unknown. This study demonstrates that layilin is highly expressed on clonally expanded CD8+ T cells in human melanoma and augments integrin-mediated cellular adhesion to enhance antitumor immunity. Tumor-infiltrating CD8+ T cells mediate antitumor immune responses. However, the mechanisms by which T cells remain poised to kill cancer cells despite expressing high levels of inhibitory receptors are unknown. Here, we report that layilin, a C-type lectin domain–containing membrane glycoprotein, is selectively expressed on highly activated, clonally expanded, but phenotypically exhausted CD8+ T cells in human melanoma. Lineage-specific deletion of layilin on murine CD8+ T cells reduced their accumulation in tumors and increased tumor growth in vivo. Congruently, gene editing of LAYN in human CD8+ T cells reduced direct tumor cell killing ex vivo. On a molecular level, layilin colocalized with integrin αLβ2 (LFA-1) on T cells, and cross-linking layilin promoted the activated state of this integrin. Accordingly, LAYN deletion resulted in attenuated LFA-1–dependent cellular adhesion. Collectively, our results identify layilin as part of a molecular pathway in which exhausted or “dysfunctional” CD8+ T cells enhance cellular adhesiveness to maintain their cytotoxic potential. |
| وصف الملف: | application/pdf |
| تدمد: | 1540-9538 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b58609bcaf697d122e5ed4e81d39d634Test https://pubmed.ncbi.nlm.nih.gov/32539073Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b58609bcaf697d122e5ed4e81d39d634 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 |
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