| Literature DB >> 27622331 |
Ilaria Marigo1, Serena Zilio2, Giacomo Desantis3, Bernhard Mlecnik4, Andrielly H R Agnellini2, Stefano Ugel5, Maria Stella Sasso2, Joseph E Qualls6, Franz Kratochvill6, Paola Zanovello7, Barbara Molon3, Carola H Ries8, Valeria Runza8, Sabine Hoves8, Amélie M Bilocq4, Gabriela Bindea4, Emilia M C Mazza9, Silvio Bicciato9, Jérôme Galon4, Peter J Murray10, Vincenzo Bronte11.
Abstract
Effective cancer immunotherapy requires overcoming immunosuppressive tumor microenvironments. We found that local nitric oxide (NO) production by tumor-infiltrating myeloid cells is important for adoptively transferred CD8(+) cytotoxic T cells to destroy tumors. These myeloid cells are phenotypically similar to inducible nitric oxide synthase (NOS2)- and tumor necrosis factor (TNF)-producing dendritic cells (DC), or Tip-DCs. Depletion of immunosuppressive, colony stimulating factor 1 receptor (CSF-1R)-dependent arginase 1(+) myeloid cells enhanced NO-dependent tumor killing. Tumor elimination via NOS2 required the CD40-CD40L pathway. We also uncovered a strong correlation between survival of colorectal cancer patients and NOS2, CD40, and TNF expression in their tumors. Our results identify a network of pro-tumor factors that can be targeted to boost cancer immunotherapies.Entities:
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Year: 2016 PMID： 27622331 PMCID： PMC5023283 DOI： 10.1016/j.ccell.2016.08.004
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743