Wallerius, MajkenWallmann, TatjanaBartish, MargaritaÖstling, JeanetteMezheyeuski, ArturTobin, Nicholas P.Nygren, EmmaPangigadde, PradeepaPellegrini, PaolaSquadrito, Mario LeonardoPontén, FredrikHartman, JohanBergh, JonasDe Milito, AngeloDe Palma, MicheleÖstman, ArneAndersson, JohnRolny, Charlotte2016-04-012016-04-012016-04-01201610.1158/0008-5472.CAN-15-2596https://infoscience.epfl.ch/handle/20.500.14299/125509WOS:000378060900009Accumulation 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.text::journal::journal article::research article