IL-10 directly activates and expands tumor-resident CD8(+) T cells without de novo infiltration from secondary lymphoid organs.

Abstract

The presence of activated intratumoral T cells correlates clinically with better prognosis in patients with cancer. Although tumor vaccines can increase the number of tumor-specific CD8(+) T cells in systemic circulation, they frequently fail to increase the number of active and tumor reactive T cells within the tumor. Here we show that treatment with the pleiotropic cytokine interleukin-10 (IL-10) induces specific activation of tumor-resident CD8(+) T cells as well as their intratumoral expansion in several mouse tumor models. We found that inhibition of T-cell trafficking from lymphoid organs did not impair IL-10-induced tumor rejection or the activation of tumor-resident CD8(+) T cells. Tumor-resident CD8(+) T cells expressed elevated levels of the IL-10 receptor and were directly activated by IL-10, resulting in prominent phosphorylation of STAT3 and STAT1. Although CD4(+) T cells, regulatory T cells, NK cells, and dendritic cells have been reported as prominent targets of IL-10 in the tumor microenvironment, we found that expression of the IL-10R was required only on CD8(+) T cells to facilitate IL-10-induced tumor rejection as well as in situ expansion and proliferation of tumor-resident CD8 T cells. Together, our findings indicate that IL-10 activates CD8(+) T-cell-mediated tumor control and suggest that IL-10 may represent a potential tumor immunotherapy in human patients with cancer.

• Authors: Jan Emmerich, John B Mumm, Ivan H Chan, Drake LaFace, Hoa Truong, Terrill McClanahan, Daniel M Gorman, Martin Oft
• Journal: Cancer research (Cancer Res) Vol. 72 Issue 14 Pg. 3570-81 (Jul 15 2012) ISSN: 1538-7445 [Electronic] United States
• PMID: 22581824 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Interleukin-10
• Interleukin-10

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology)
• Female
• Humans
• Interleukin-10 (pharmacology)
• Lymphatic System (immunology)
• Lymphocyte Activation (drug effects, immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Neoplasms (immunology)
• Receptors, Interleukin-10 (metabolism)
• T-Lymphocytes, Regulatory (immunology)