NKG2A is a late immune checkpoint on CD8 T cells and marks repeated stimulation and cell division
| العنوان: | NKG2A is a late immune checkpoint on CD8 T cells and marks repeated stimulation and cell division |
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| المؤلفون: | Mandy van Gulijk, Marit J van Elsas, Nadine van Montfoort, Thorbald van Hall, Pornpimol Charoentong, Marjolein Sluijter, Sjoerd H. van der Burg, Gregor Sturm, Zlatko Trajanoski, Saskia J. A. M. Santegoets, Francesca Finotello, Linda Borst, Szymon M. Kielbasa, Christianne Groeneveldt |
| المساهمون: | Pulmonary Medicine |
| المصدر: | International Journal of Cancer, 150(4), 688-704. WILEY International Journal of Cancer, 150(4), 688-704. Wiley-Liss Inc. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Cancer Research, Receptor expression, Receptors, Antigen, T-Cell, CD8 T cells, Biology, CD8-Positive T-Lymphocytes, NKG2A, 03 medical and health sciences, Mice, 0302 clinical medicine, Artificial antigen presenting cells, Lymphocytes, Tumor-Infiltrating, TIGIT, Antigen, SDG 3 - Good Health and Well-being, Antigens, CD, Transforming Growth Factor beta, Tumor Microenvironment, Cytotoxic T cell, Animals, Humans, TGF-beta, Receptors, Immunologic, Receptor, Hepatitis A Virus Cellular Receptor 2, immune checkpoint, 030304 developmental biology, 0303 health sciences, T-cell receptor, Immune Checkpoint Proteins, Lymphocyte Activation Gene 3 Protein, Immune checkpoint, Cell biology, tumor immunity, Mice, Inbred C57BL, Oncology, 030220 oncology & carcinogenesis, NK Cell Lectin-Like Receptor Subfamily C, Cell Division |
| الوصف: | The surface inhibitory receptor NKG2A forms heterodimers with the invariant CD94 chain and is expressed on a subset of activated CD8 T cells. As antibodies to block NKG2A are currently tested in several efficacy trials for different tumor indications, it is important to characterize the NKG2A+ CD8 T cell population in the context of other inhibitory receptors. Here we used a well-controlled culture system to study the kinetics of inhibitory receptor expression. Naïve mouse CD8 T cells were synchronously and repeatedly activated by artificial antigen presenting cells in the presence of the homeostatic cytokine IL-7. The results revealed NKG2A as a late inhibitory receptor, expressed after repeated cognate antigen stimulations. In contrast, the expression of PD-1, TIGIT and LAG-3 was rapidly induced, hours after first contact and subsequently down regulated during each resting phase. This late, but stable expression kinetics of NKG2A was most similar to that of TIM-3 and CD39. Importantly, single-cell transcriptomics of human tumor-infiltrating lymphocytes (TILs) showed indeed that these receptors were often coexpressed by the same CD8 T cell cluster. Furthermore, NKG2A expression was associated with cell division and was promoted by TGF-β in vitro, although TGF-β signaling was not necessary in a mouse tumor model in vivo. In summary, our data show that PD-1 reflects recent TCR triggering, but that NKG2A is induced after repeated antigen stimulations and represents a late inhibitory receptor. Together with TIM-3 and CD39, NKG2A might thus mark actively dividing tumor-specific TILs. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0020-7136 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da18243b002dd87600ce266a3e11728fTest http://hdl.handle.net/1887/3264396Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....da18243b002dd87600ce266a3e11728f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00207136 |
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