Autor: |
Carola Ries, Amélie M. Bilocq, Barbara Molon, Andrielly H. R. Agnellini, Franz Kratochvill, Bernhard Mlecnik, Jérôme Galon, Valeria Runza, Emilia Maria Cristina Mazza, Vincenzo Bronte, Giacomo Desantis, Ilaria Marigo, Sabine Hoves, Maria Stella Sasso, Joseph E. Qualls, Silvio Bicciato, Gabriela Bindea, Stefano Ugel, Peter J. Murray, Serena Zilio, Paola Zanovello |
Jazyk: |
angličtina |
Rok vydání: |
2016 |
Předmět: |
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Popis: |
Summary 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. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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