Journal
CLINICAL IMMUNOLOGY
Volume 154, Issue 2, Pages 116-126Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2014.07.005
Keywords
Interleukin 22; Chemoresistance; STAT3; Interleukin 8
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Funding
- National Natural Science Foundation of China [81372636, 81302089]
- National High Technology Research and Development Program of China (863 Program) [SQ2014SFOZD00314]
- Shanghai Young Teacher Training Program [jdy11080, ZZjdyx13074]
- Shanghai Jiaotong University School of Medicine Research Funding [11qy003]
- Shanghai Health Bureau Research Funding [20114221]
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Resistance to chemotherapy is the major cause of colorectal cancer (CRC) treatment failure. The cytokine IL-22, which is produced by T cells and HK cells, is associated with tumorigenesis and tumor progression in cancers. However, the role of IL-22 in chemoresistance has not been investigated. We found that IL-22 levels in tumor tissues and peripheral blood were associated with chemoresistance and indicate poor prognosis for patients who received FOLFOX chemotherapy. In CRC cells, IL-22 was able to attenuate the cytotoxic and apoptosis-inducing effects of 5-FU and OXA by activating the STAT3 pathway and subsequently increasing the expression of anti-apoptotic genes. In addition, IL-22 conferred resistance to 5-FU and OXA by inducing IL-8 autocrine expression through STAT3 activation. Our findings identify IL-22 as a novel chemoresistance cytokine and may be a useful prognostic biomarker for CRC patients receiving FOLFOX chemotherapy. (C) 2014 Elsevier Inc. All rights reserved.
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