| Title: |
Divergent local and systemic antitumor response in primary uveal melanomas |
| Authors: |
Lucibello, Francesca; Lalanne, Ana I.; Le Gac, Anne-Laure; Soumare, Abdoulaye; Aflaki, Setareh; Cyrta, Joanna; Dubreuil, Lea; Mestdagh, Martin; Salou, Marion; Houy, Alexandre; Ekwegbara, Christina; Jamet, Camille; Gardrat, Sophie; Le Ven, Anais; Bernardeau, Karine; Cassoux, Nathalie; Matet, Alexandre; Malaise, Denis; Pierron, Gaelle; Piperno-Neumann, Sophie; Stern, Marc-Henri; Rodrigues, Manuel; Lantz, Olivier |
| Contributors: |
Agence Nationale de la Recherche; ITMO-Cancer Aviesann; SiRIC-Curie; Institut National de la Santé et de la Recherche Médicale; Institut Curie; Ligue contre le Cancer; French Government; Canceropole Ile-de-France; European Union’s Horizon 2020 research and innovation; SIRIC2 |
| Source: |
Journal of Experimental Medicine ; volume 221, issue 6 ; ISSN 0022-1007 1540-9538 |
| Publisher Information: |
Rockefeller University Press |
| Publication Year: |
2024 |
| Description: |
Uveal melanoma (UM) is the most common cancer of the eye. The loss of chromosome 3 (M3) is associated with a high risk of metastases. M3 tumors are more infiltrated by T-lymphocytes than low-risk disomic-3 (D3) tumors, contrasting with other tumor types in which T cell infiltration correlates with better prognosis. Whether these T cells represent an antitumor response and how these T cells would be primed in the eye are both unknown. Herein, we characterized the T cells infiltrating primary UMs. CD8+ and Treg cells were more abundant in M3 than in D3 tumors. CD39+PD-1+CD8+ T cells were enriched in M3 tumors, suggesting specific responses to tumor antigen (Ag) as confirmed using HLA-A2:Melan-A tetramers. scRNAseq-VDJ analysis of T cells evidenced high numbers of proliferating CD39+PD1+CD8+ clonal expansions, suggesting in situ antitumor Ag responses. TCRseq and tumor-Ag tetramer staining characterized the recirculation pattern of the antitumor responses in M3 and D3 tumors. Thus, tumor-Ag responses occur in localized UMs, raising the question of the priming mechanisms in the absence of known lymphatic drainage. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1084/jem.20232094 |
| DOI: |
10.1084/jem.20232094/1927991/jem_20232094.pdf |
| Availability: |
https://doi.org/10.1084/jem.20232094; https://rupress.org/jem/article-pdf/doi/10.1084/jem.20232094/1927991/jem_20232094.pdf |
| Rights: |
http://www.rupress.org/terms/ ; https://creativecommons.org/licenses/by-nc-sa/4.0/ |
| Accession Number: |
edsbas.44F3CA8A |
| Database: |
BASE |