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CD30L/CD30 signaling regulates the formation of the tumor immune microenvironment and inhibits intestinal tumor development of colitis-associated colon cancer in mice.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2020 Jul; Vol. 84, pp. 106531. Date of Electronic Publication: 2020 Apr 27. - Publication Year :
- 2020
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Abstract
- Inflammatory bowel disease is one of the major causes of colitis-associated colon cancer (CAC). Therefore, it is necessary to explore new therapies to prevent colon cancer (CRC) in view of the relationship between chronic inflammation and tumor development. Previous studies on the correlation between CD30L/CD30 and cancer were mostly limited to lymphoid or homogenous tumors, while there have been only a few reports on the role of CD30L/CD30 signal transduction in the pathogenesis of CAC. In this study, we established an AOM/DSS-induced CAC model with CD30LKO mice to explore the effect of CD30L/CD30 signal transduction on the formation of the intestinal tumor immune microenvironment (TIME) during the development of intestinal tumors. Our results revealed that CD30L deficiency promoted the accumulation of myeloid derived suppressor cells (MDSCs), increased the expression of PD-L1 on MDSCs and tumor associated macrophages (TAMs), and enhanced the secretion of various inflammatory and immunosuppressive factors in the intestinal mucosa of CAC mice. Furthermore, CD30L gene deletion could selectively promote the upregulation of PD-1 expression on CD4 <superscript>+</superscript> and CD8 <superscript>+</superscript> T cells and inhibit their activation, differentiation and secretion of effector cytokines, which led to an attenuation of antitumor immune responses mediated by T <subscript>EM</subscript> (CD44 <superscript>+</superscript> CD62L <superscript>-</superscript> ) cells. Thus, our data suggest that CD30L/CD30 signaling might be a potential candidate target for immunological therapy in CAC.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Azoxymethane
CD30 Ligand genetics
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Carcinogens
Colitis chemically induced
Colitis complications
Colitis-Associated Neoplasms etiology
Dextran Sulfate
Female
Intestines immunology
Ki-1 Antigen genetics
Male
Mice, Inbred C57BL
Mice, Knockout
Signal Transduction drug effects
Tumor Microenvironment drug effects
Tumor Microenvironment immunology
CD30 Ligand immunology
Colitis immunology
Colitis-Associated Neoplasms immunology
Ki-1 Antigen immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 84
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 32353687
- Full Text :
- https://doi.org/10.1016/j.intimp.2020.106531