Expression of LLT1 and its receptor CD161 in lung cancer is associated with better clinical outcome
| Title: | Expression of LLT1 and its receptor CD161 in lung cancer is associated with better clinical outcome |
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| Authors: | Véronique M. Braud, Jérôme Biton, Etienne Becht, Samantha Knockaert, Audrey Mansuet-Lupo, Estelle Cosson, Diane Damotte, Marco Alifano, Pierre Validire, Fabienne Anjuère, Isabelle Cremer, Nicolas Girard, Dominique Gossot, Agathe Seguin-Givelet, Marie-Caroline Dieu-Nosjean, Claire Germain |
| Source: | OncoImmunology, Vol 7, Iss 5 (2018) |
| Publisher Information: | Taylor & Francis Group, 2018. |
| Publication Year: | 2018 |
| Collection: | LCC:Immunologic diseases. Allergy LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: | llt1, cd161, non-small cell lung cancer, tertiary lymphoid structures, germinal center, tumor-infiltrating lymphocytes, co-stimulatory receptor, th1 response, immune checkpoints, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: | Co-stimulatory and inhibitory receptors expressed by immune cells in the tumor microenvironment modulate the immune response and cancer progression. Their expression and regulation are still not fully characterized and a better understanding of these mechanisms is needed to improve current immunotherapies. Our previous work has identified a novel ligand/receptor pair, LLT1/CD161, that modulates immune responses. Here, we extensively characterize its expression in non-small cell lung cancer (NSCLC). We show that LLT1 expression is restricted to germinal center (GC) B cells within tertiary lymphoid structures (TLS), representing a new hallmark of the presence of active TLS in the tumor microenvironment. CD161-expressing immune cells are found at the vicinity of these structures, with a global enrichment of NSCLC tumors in CD161+ CD4+ and CD8+ T cells as compared to normal distant lung and peripheral blood. CD161+ CD4+ T cells are more activated and produce Th1-cytokines at a higher frequency than their matched CD161-negative counterparts. Interestingly, CD161+ CD4+ T cells highly express OX40 co-stimulatory receptor, less frequently 4-1BB, and display an activated but not completely exhausted PD-1-positive Tim-3-negative phenotype. Finally, a meta-analysis revealed a positive association of CLEC2D (coding for LLT1) and KLRB1 (coding for CD161) gene expression with favorable outcome in NSCLC, independently of the size of T and B cell infiltrates. These data are consistent with a positive impact of LLT1/CD161 on NSCLC patient survival, and make CD161-expressing CD4+ T cells ideal candidates for efficient anti-tumor recall responses. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2162-402X 2162402X |
| Relation: | https://doaj.org/toc/2162-402X |
| DOI: | 10.1080/2162402X.2017.1423184 |
| Access URL: | https://doaj.org/article/164e7738449c4dea95192ede491c7aff |
| Accession Number: | edsdoj.164e7738449c4dea95192ede491c7aff |
| Database: | Directory of Open Access Journals |
| ISSN: | 2162402X |
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| DOI: | 10.1080/2162402X.2017.1423184 |
| Published in: | OncoImmunology |
| Language: | English |