2. Academic Validation
  3. CD30L/CD30 signaling regulates the formation of the tumor immune microenvironment and inhibits intestinal tumor development of colitis-associated colon cancer in mice

CD30L/CD30 signaling regulates the formation of the tumor immune microenvironment and inhibits intestinal tumor development of colitis-associated colon cancer in mice

  • Int Immunopharmacol. 2020 Jul;84:106531. doi: 10.1016/j.intimp.2020.106531.
Xiao Wang 1,  Yaxian Gao 2,  Xiaoqing Zhang 1,  Xiaonan Wang 1,  Biao Wang 3,  Xin Meng 3,  Yasunobu Yoshikai 4,  Yuanyuan Wang 5,  Xun Sun 6
Affiliations

Affiliations

  • 1 Department of Immunology, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, PR China.
  • 2 Department of Immunology, Chengde Medical College, Chengde, Hebei 067000, PR China; Department of Immunology, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, PR China.
  • 3 Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences of China Medical University, Shenyang, Liaoning Province, PR China.
  • 4 Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
  • 5 Department of Anesthesiology, The Fourth Affiliated Hospital, China Medical University, Shenyang, Liaoning Province, PR China. Electronic address: shetao1220@hotmail.com.
  • 6 Department of Immunology, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, PR China. Electronic address: wsunxun1220@cmu.edu.cn.
PMID: 32353687 DOI: 10.1016/j.intimp.2020.106531
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+ and CD8+ T cells and inhibit their activation, differentiation and secretion of effector cytokines, which led to an attenuation of antitumor immune responses mediated by TEM (CD44+CD62L-) cells. Thus, our data suggest that CD30L/CD30 signaling might be a potential candidate target for immunological therapy in CAC.

Keywords

CD30L/CD30; Colitis-associated colon cancer; MDSC; T cells; TAM; Tumor immune microenvironment.

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