BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties
| Autor: | Laszlo Radvanyi, Krit Ritthipichai, Marie Andrée Forget, Richard Wu, Patrick Hwu, Jie Qing Chen, Hui Liu, Cara Haymaker, Chantale Bernatchez, Ena Wang, Francesco M. Marincola |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Tumor-infiltrating lymphocytes
Melanoma medicine.medical_treatment Immunology BTLA chemical and pharmacologic phenomena Biology medicine.disease Cell therapy CD8+ effector-memory Cytokine T cell survival/persistence Oncology Apoptosis tumor-infiltrating lymphocytes medicine melanoma Immunology and Allergy Protein kinase B CD8 B- and T-lymphocyte attenuator Original Research |
| Zdroj: | Oncoimmunology |
| ISSN: | 2162-402X 2162-4011 |
| Popis: | In a recent adoptive cell therapy (ACT) clinical trial using autologous tumor-infiltrating lymphocytes (TILs) in patients with metastatic melanoma, we found an association between CD8+ T cells expressing the inhibitory receptor B- and T-lymphocyte attenuator (BTLA) and clinical response. Here, we further characterized this CD8+BTLA+ TIL subset and their CD8+BTLA- counterparts. We found that the CD8+ BTLA+ TILs had an increased response to IL-2, were less-differentiated effector-memory (TEM) cells, and persisted longer in vivo after infusion. In contrast, CD8+BTLA- TILs failed to proliferate and expressed genes associated with T-cell deletion/tolerance. Paradoxically, activation of BTLA signaling by its ligand, herpes virus entry mediator (HVEM), inhibited T-cell division and cytokine production, but also activated the Akt/PKB pathway thus protecting CD8+BTLA+ TILs from apoptosis. Our results point to a new role of BTLA as a useful T-cell differentiation marker in ACT and a dual signaling molecule that curtails T-cell activation while also conferring a survival advantage for CD8+ T cells. These attributes may explain our previous observation that BTLA expression on CD8+ TILs correlates with clinical response to adoptive T-cell therapy in metastatic melanoma. |
| Databáze: | OpenAIRE |
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