Paradoxical Roles of IL-4 in Tumor Immunity

Li, Chi Kong; Chen, Lin; Qin, Zhihai

doi:10.1038/cmi.2009.53

Cited by 125 publications

(97 citation statements)

References 67 publications

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“…Among these cytokines, IL-4 has been shown to have both protective as well as suppressive effect of antitumor immune responses, depending on the source of this cytokine and also the time of its production (30). Recently, it has been reported that IL-4 can downregulate the NKG2D expression on human CD8 + T as well as mouse NK cells, resulting in suppression of antitumor immune responses (31,32).…”

Section: G D T Cells Have Many Unique Features and Functions (1-6)mentioning

confidence: 99%

Regulatory Role of Vγ1 γδ T Cells in Tumor Immunity through IL-4 Production

Hao

Dong

Xia

et al. 2011

The Journal of Immunology

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It has been demonstrated that the two main subsets of peripheral γδ T cells, Vγ1 and Vγ4, have divergent functions in many diseases models. Recently, we reported that Vγ4 γδ T cells played a protective role in tumor immunity through eomesodermin-controlled mechanisms. However, the precise roles of Vγ1 γδ T cells in tumor immunity, especially whether Vγ1 γδ T cells have any interaction with Vγ4 γδ T cells, remain unknown. We demonstrated in this paper that Vγ1 γδ T cells suppressed Vγ4 γδ T cell-mediated antitumor function both in vitro and in vivo, and this suppression was cell contact independent. Using neutralizing anti–IL-4 Ab or IL-4−/− mice, we determined the suppressive factor derived from Vγ1 γδ T cells was IL-4. Indeed, treatment of Vγ4 γδ T cells with rIL-4 significantly reduced expression levels of NKG2D, perforin, and IFN-γ. Finally, Vγ1 γδ T cells produced more IL-4 and expressed significantly higher level of GATA-3 upon Th2 priming in comparison with Vγ4 γδ T cells. Therefore, to our knowledge, our results established for the first time a negative regulatory role of Vγ1 γδ T cells in Vγ4 γδ T cell-mediated antitumor immunity through cell contact-independent and IL-4–mediated mechanisms. Selective depletion of this suppressive subset of γδ T cells may be beneficial for tumor immune therapy.

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Section: G D T Cells Have Many Unique Features and Functions (1-6)mentioning

confidence: 99%

Regulatory Role of Vγ1 γδ T Cells in Tumor Immunity through IL-4 Production

Hao

Dong

Xia

et al. 2011

The Journal of Immunology

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“…It is very likely that the effects of IL-4 are dependent on the types of its source and target cells, the concentration and time of expression, the availability of the signaling components and regulatory pathways in target cells, and other interacting microenvironmental factors; some of these aspects have been previously reviewed. 91,92 Here we summarize the current knowledge of the opposing anti-and pro-tumor effects which IL-4 exerts on different target cells (Fig. 3).…”

Section: Opposing Effects Of Il-4 On Tumor Growthmentioning

confidence: 99%

Alternative activation of tumor-associated macrophages by IL-4

2010

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“…In our results, IL4 was seen to be involved with complete remission when treated with any of the three therapies: mitotic inhibitors, anti-angiogenesis and antimetabolite. This was validated further with the experimental evidence of overexpressed IL4R contributing towards remission in lung cancer patients [97].…”

Section: Survival Analysis and Biomarkersmentioning

confidence: 99%