T cell-derived IL-10 promotes lung cancer growth by suppressing both T cell and APC function.
We have found previously that human lung cancers potently induce T lymphocyte IL-10 production in vitro. To assess the impact of enhanced T cell-derived IL-10 on antitumor immunity in vivo, we utilized transgenic mice expressing IL-10 under the control of the IL-2 promoter. We have shown previously that Lewis lung carcinoma cells (3LL) have more aggressive growth potential in IL-10 transgenic mice compared with control littermates. In this study, we show that transfer of T cells from IL-10 transgenic mice to control littermates transferred the IL-10 immunosuppressive effect and led to enhanced 3LL tumor growth. In addition to changes in T cell-mediated immunity, professional APC from IL-10 transgenic mice were found to have significantly suppressed capacity to induce MHC alloreactivity, CTL responses, and IL-12 production. Tumor Ag-pulsed dendritic cells from IL-10 transgenic mice also failed to generate antitumor reactivity. These results suggest that increased levels of T cell-derived IL-10 severely impair antitumor immunity in vivo, due to defects in both T cell and APC function.
Sharma
S
S
University of California, Los Angeles-Wadsworth Pulmonary Laboratory, School of Medicine, West Los Angeles Veterans Affairs Medical Center 90073, USA.
Stolina
M
M
Lin
Y
Y
Gardner
B
B
Miller
P W
PW
Kronenberg
M
M
Dubinett
S M
SM
D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000172:deficiency; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016207:Cytokines; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D018664:Interleukin-12