Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells

Giovanna Gallina, Luigi Dolcetti, Paolo Serafini, Carmela De Santo, Ilaria Marigo, Mario P. Colombo, Giuseppe Basso, Frank Brombacher, Ivan Borrello, Paola Zanovello, Silvio Bicciato, Vincenzo Bronte

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Abstract

Active suppression of tumor-specific T lymphocytes can limit the efficacy of immune surveillance and immunotherapy. While tumor-recruited CD11b + myeloid cells are known mediators of tumor-associated immune dysfunction, the true nature of these suppressive cells and the fine biochemical pathways governing their immunosuppressive activity remain elusive. Here we describe a population of circulating CD11b+IL-4 receptor α+ (CD11b+IL-4Rα+), inflammatory-type monocytes that is elicited by growing tumors and activated by IFN-γ released from T lymphocytes. CD11b+IL- 4Rα+ cells produced IL-13 and IFN-γ and integrated the downstream signals of these cytokines to trigger the molecular pathways suppressing antigen-activated CD8+ T lymphocytes. Analogous immunosuppressive circuits were active in CD11b+ cells present within the tumor microenvironment. These suppressor cells challenge the current idea that tumor-conditioned immunosuppressive monocytes/macrophages are alternatively activated. Moreover, our data show how the inflammatory response elicited by tumors had detrimental effects on the adaptive immune system and suggest novel approaches for the treatment of tumor-induced immune dysfunctions.

Original languageEnglish
Pages (from-to)2777-2790
Number of pages14
JournalJournal of Clinical Investigation
Volume116
Issue number10
DOIs
Publication statusPublished - Oct 2 2006

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Immunosuppressive Agents
Monocytes
T-Lymphocytes
Neoplasms
Interleukin-4 Receptors
CD8 Antigens
Tumor Microenvironment
Interleukin-13
Myeloid Cells
Immunotherapy
Immune System
Macrophages
Cytokines
Population

ASJC Scopus subject areas

  • Medicine(all)

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Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells. / Gallina, Giovanna; Dolcetti, Luigi; Serafini, Paolo; De Santo, Carmela; Marigo, Ilaria; Colombo, Mario P.; Basso, Giuseppe; Brombacher, Frank; Borrello, Ivan; Zanovello, Paola; Bicciato, Silvio; Bronte, Vincenzo.

In: Journal of Clinical Investigation, Vol. 116, No. 10, 02.10.2006, p. 2777-2790.

Research output: Contribution to journalArticle

Gallina, G, Dolcetti, L, Serafini, P, De Santo, C, Marigo, I, Colombo, MP, Basso, G, Brombacher, F, Borrello, I, Zanovello, P, Bicciato, S & Bronte, V 2006, 'Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells', Journal of Clinical Investigation, vol. 116, no. 10, pp. 2777-2790. https://doi.org/10.1172/JCI28828
Gallina, Giovanna ; Dolcetti, Luigi ; Serafini, Paolo ; De Santo, Carmela ; Marigo, Ilaria ; Colombo, Mario P. ; Basso, Giuseppe ; Brombacher, Frank ; Borrello, Ivan ; Zanovello, Paola ; Bicciato, Silvio ; Bronte, Vincenzo. / Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells. In: Journal of Clinical Investigation. 2006 ; Vol. 116, No. 10. pp. 2777-2790.
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