Open AccessJournal Article
T Cell-Derived IL-10 Promotes Lung Cancer Growth by Suppressing Both T Cell and APC Function
Sherven Sharma,Marina Stolina,Ying Lin,Brian Gardner,Patrice W. Miller,Mitchell Kronenberg,Steven M. Dubinett +6 more
TLDR
It is suggested 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.Abstract:
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.read more
Citations
More filters
Journal ArticleDOI
Interleukin-10 and the interleukin-10 receptor.
TL;DR: Findings that have advanced the understanding of IL-10 and its receptor are highlighted, as well as its in vivo function in health and disease.
Journal ArticleDOI
Natural selection of tumor variants in the generation of “tumor escape” phenotypes
TL;DR: The idea that tumors must “escape” from immune recognition contains the implicit assumption that tumors can be destroyed by immune responses either spontaneously or as the result of immunotherapeutic intervention.
Journal ArticleDOI
Mechanisms and functional significance of tumour-induced dendritic-cell defects.
TL;DR: This article focuses on the functional consequences and recently described mechanisms of the dendritic-cell defects in cancer.
Journal ArticleDOI
Dual Blockade of PD-1 and CTLA-4 Combined with Tumor Vaccine Effectively Restores T-Cell Rejection Function in Tumors
TL;DR: It is indicated thatPD-1 signaling in tumors is required for both suppressing effector T cells and maintaining tumor Tregs, and that PD-1/PD-L1 pathway (CD274) blockade augments tumor inhibition by increasing effectors T-cell activity, thereby attenuating Treg suppression.
Journal ArticleDOI
IL-6 Regulates In Vivo Dendritic Cell Differentiation through STAT3 Activation
Sung Joo Park,Takayuki Nakagawa,Hidemitsu Kitamura,Toru Atsumi,Hokuto Kamon,Shinichiro Sawa,Daisuke Kamimura,Naoko Ueda,Yoichiro Iwakura,Katsuhiko Ishihara,Masaaki Murakami,Toshio Hirano +11 more
TL;DR: IL-6 is a potent regulator of DC differentiation in vivo, and IL-6-gp130-STAT3 signaling in DCs may represent a critical target for controlling T cell-mediated immune responses in vivo.
References
More filters
Journal ArticleDOI
The dendritic cell system and its role in immunogenicity
TL;DR: Dendritic cells are specialized to mediate several physiologic components of immunogenicity such as the acquisition of antigens in tissues, the migration to lymphoid organs, and the identification and activation of antigen-specific T cells.
Journal ArticleDOI
A CD4 + T-cell subset inhibits antigen-specific T-cell responses and prevents colitis
Hervé Groux,Anne O'Garra,M. Bigler,Matthieu Rouleau,Svetlana Antonenko,Jan E. de Vries,Maria Grazia Roncarolo +6 more
TL;DR: It is shown that chronic activation of both human and murine CD4+T cells in the presence of interleukin (IL)-10 gives rise to CD4-T-cell clones with low proliferative capacity, producing high levels ofIL-10, low levels of IL-2 and no IL-4.
Journal Article
IL-10 inhibits cytokine production by activated macrophages.
TL;DR: The potent action of IL-10 on the macrophage, particularly at the level of monokine production, supports an important role for this cytokine not only in the regulation of T cell responses but also in acute inflammatory responses.
Journal ArticleDOI
Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression.
R de Waal Malefyt,John B. A. G. Haanen,H Spits,M G Roncarolo,A.A. te Velde,Carl G. Figdor,K E Johnson,Rob A. Kastelein,Hans Yssel,J E de Vries +9 more
TL;DR: It is indicated that IL-10 and v-IL-10 can completely prevent antigen-specific T cell proliferation by inhibition of the antigen-presenting capacity of monocytes through downregulation of class II MHC antigens on monocytes.
Journal Article
IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells.
David Fiorentino,Albert Zlotnik,Pedro L. Vieira,Tim R. Mosmann,M Howard,Kevin W. Moore,Anne O'Garra +6 more
TL;DR: IL-10 may inhibit macrophage accessory cell function which is independent of TCR-class II MHC interactions, as well as inhibits IL-2-induced IFN-gamma production by Th1 cells in an Ag-free system requiring only the presence of accessory cells.