T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells

Ilaria Marigo; Serena Zilio; Giacomo Desantis; Bernhard Mlecnik; Andrielly H R Agnellini; Stefano Ugel; Maria Stella Sasso; Joseph E. Qualls; Franz Kratochvill; Paola Zanovello; Barbara Molon; Carola H. Ries; Valeria Runza; Sabine Hoves; Amélie M. Bilocq; Gabriela Bindea; Emilia M C Mazza; Silvio Bicciato; Jérôme Galon; Peter J. Murray; Vincenzo Bronte

doi:10.1016/j.ccell.2016.08.004

T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells

Ilaria Marigo, Serena Zilio, Giacomo Desantis, Bernhard Mlecnik, Andrielly H R Agnellini, Stefano Ugel, Maria Stella Sasso, Joseph E. Qualls, Franz Kratochvill, Paola Zanovello, Barbara Molon, Carola H. Ries, Valeria Runza, Sabine Hoves, Amélie M. Bilocq, Gabriela Bindea, Emilia M C Mazza, Silvio Bicciato, Jérôme Galon, Peter J. MurrayVincenzo Bronte

Istituto Oncologico Veneto

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	377-390
Number of pages	14
Journal	Cancer Cell
Volume	30
Issue number	3
DOIs	https://doi.org/10.1016/j.ccell.2016.08.004
Publication status	Published - Sept 12 2016

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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10.1016/j.ccell.2016.08.004

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Marigo, I., Zilio, S., Desantis, G., Mlecnik, B., Agnellini, A. H. R., Ugel, S., Sasso, M. S., Qualls, J. E., Kratochvill, F., Zanovello, P., Molon, B., Ries, C. H., Runza, V., Hoves, S., Bilocq, A. M., Bindea, G., Mazza, E. M. C., Bicciato, S., Galon, J., ... Bronte, V. (2016). T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells. Cancer Cell, 30(3), 377-390. https://doi.org/10.1016/j.ccell.2016.08.004

Marigo, I, Zilio, S, Desantis, G, Mlecnik, B, Agnellini, AHR, Ugel, S, Sasso, MS, Qualls, JE, Kratochvill, F, Zanovello, P, Molon, B, Ries, CH, Runza, V, Hoves, S, Bilocq, AM, Bindea, G, Mazza, EMC, Bicciato, S, Galon, J, Murray, PJ & Bronte, V 2016, 'T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells', Cancer Cell, vol. 30, no. 3, pp. 377-390. https://doi.org/10.1016/j.ccell.2016.08.004

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title = "T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells",

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.",

author = "Ilaria Marigo and Serena Zilio and Giacomo Desantis and Bernhard Mlecnik and Agnellini, {Andrielly H R} and Stefano Ugel and Sasso, {Maria Stella} and Qualls, {Joseph E.} and Franz Kratochvill and Paola Zanovello and Barbara Molon and Ries, {Carola H.} and Valeria Runza and Sabine Hoves and Bilocq, {Am{\'e}lie M.} and Gabriela Bindea and Mazza, {Emilia M C} and Silvio Bicciato and J{\'e}r{\^o}me Galon and Murray, {Peter J.} and Vincenzo Bronte",

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doi = "10.1016/j.ccell.2016.08.004",

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T1 - T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells

AU - Marigo, Ilaria

AU - Zilio, Serena

AU - Desantis, Giacomo

AU - Mlecnik, Bernhard

AU - Agnellini, Andrielly H R

AU - Ugel, Stefano

AU - Sasso, Maria Stella

AU - Qualls, Joseph E.

AU - Kratochvill, Franz

AU - Zanovello, Paola

AU - Molon, Barbara

AU - Ries, Carola H.

AU - Runza, Valeria

AU - Hoves, Sabine

AU - Bilocq, Amélie M.

AU - Bindea, Gabriela

AU - Mazza, Emilia M C

AU - Bicciato, Silvio

AU - Galon, Jérôme

AU - Murray, Peter J.

AU - Bronte, Vincenzo

PY - 2016/9/12

Y1 - 2016/9/12

N2 - 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.

AB - 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.

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T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells

Abstract

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