Heterotypic cellular and molecular interactions in the tumor microenvironment (TME) control cancer progression. Here, we show that CD1d-restricted invariant natural killer (iNKT) cells control prostate cancer (PCa) progression by sculpting the TME. In a mouse PCa model, iNKT cells restrained the pro-angiogenic and immunosuppressive capabilities of tumor-infiltrating immune cells by reducing pro-angiogenic TIE2+, M2-like macrophages (TEMs), and sustaining pro-inflammatory M1-like macrophages. iNKT cells directly contacted macrophages in the PCa stroma, and iNKT cell transfer into tumor-bearing mice abated TEMs, delaying tumor progression. iNKT cells modulated macrophages through the cooperative engagement of CD1d, Fas, and CD40, which promoted selective killing of M2-like and survival of M1-like macrophages. Human PCa aggressiveness associate with reduced intra-tumoral iNKT cells, increased TEMs, and expression of pro-angiogenic genes, underscoring the clinical significance of this crosstalk. Therefore, iNKT cells may control PCa through mechanisms involving differential macrophage modulation, which may be harnessed for therapeutically reprogramming the TME. Cortesi et al. provide evidence that iNKT cells contribute to cancer immune surveillance. Due to differential tuning of tumor-associated macrophage populations, iNKT cells remodel the microenvironment of prostate cancer, enforcing a tumor-opposing state that controls tumor progression.
Bimodal CD40/Fas-Dependent Crosstalk between iNKT Cells and Tumor-Associated Macrophages Impairs Prostate Cancer Progression / F. Cortesi, G. Delfanti, A. Grilli, A. Calcinotto, F. Gorini, F. Pucci, R. Lucianò, M. Grioni, A. Recchia, F. Benigni, A. Briganti, A. Salonia, M. De Palma, S. Bicciato, C. Doglioni, M. Bellone, G. Casorati, P. Dellabona. - In: CELL REPORTS. - ISSN 2211-1247. - 22:11(2018 Mar 13), pp. 3006-3020.
|Titolo:||Bimodal CD40/Fas-Dependent Crosstalk between iNKT Cells and Tumor-Associated Macrophages Impairs Prostate Cancer Progression|
|Parole Chiave:||angiogenesis; CD1d; CD40; Fas; immunotherapy; iNKT cells; macrophage; prostate cancer; tumor microenvironment; Biochemistry, Genetics and Molecular Biology (all)|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
Settore BIO/13 - Biologia Applicata
|Data di pubblicazione:||13-mar-2018|
|Data ahead of print / Data di stampa:||13-mar-2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.celrep.2018.02.058|
|Appare nelle tipologie:||01 - Articolo su periodico|