Êtes-vous un étudiant de l'EPFL à la recherche d'un projet de semestre?
Travaillez avec nous sur des projets en science des données et en visualisation, et déployez votre projet sous forme d'application sur Graph Search.
Accumulation of tumor-associated macrophages (TAM) correlates with malignant progression, immune suppression and poor prognosis. In this study, we defined a critical role for the cell-surface guidance molecule SEMA3A in differential proliferative control of TAMs. Tumor cell-derived SEMA3A restricted the proliferation of pro-tumoral M2 macrophages but increased the proliferation of anti-tumoral M1, acting through the SEMA3A receptor neuropilin-1 (NP1). Expansion of M1 macrophages in vivo enhanced the recruitment and activation of NK cells and cytotoxic CD8+ T cells to tumors, inhibiting their growth. In human breast cancer specimens, we found that immunohistochemical levels of SEMA3A correlated with the expression of genes characteristic of M1 macrophages, CD8+ T cells and NK cells, while inversely correlating with established characters of malignancy. In summary, our results illuminate a mechanism whereby the TAM phenotype is controlled, and identify the cell surface molecule SEMA3A as a candidate for therapeutic targeting.
Didier Trono, Priscilla Turelli, Evaristo Jose Planet Letschert, Filipe Amândio Brandão Sanches Vong Martins, Florian Huber, Olga Marie Louise Rosspopoff, Romain Forey, Sandra Eloise Kjeldsen, Cyril David Son-Tuyên Pulver, Joana Carlevaro Fita