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C‐C chemokine hepatocellular carcinoma motif ligand 5 ‐deficiency promotes hepatocellular carcinoma progression by affecting B cell recruitment
Author(s) -
Li Xiang,
Han Qiu Cheng,
Yu Chang,
Luo Yi Chun,
Wang Fang,
Sun Xue Hua,
Gao Yue Qiu,
Tan Wei Feng,
Xia Qiang
Publication year - 2021
Publication title -
journal of digestive diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 51
eISSN - 1751-2980
pISSN - 1751-2972
DOI - 10.1111/1751-2980.12997
Subject(s) - ccl5 , chemokine , hepatocellular carcinoma , immune system , flow cytometry , cancer research , tumor microenvironment , peripheral blood mononuclear cell , metastasis , cell , t cell , immunology , microbiology and biotechnology , medicine , biology , cancer , il 2 receptor , biochemistry , in vitro , genetics
Objective To evaluate the expression of C‐C motif chemokine ligand 5 (CCL5) in hepatocellular carcinoma (HCC) and to explore its role in regulating the immune microenvironment and the related mechanism in tumor immunity. Methods The mRNA expression level of CCL5 in HCC and adjacent non‐cancerous tissues was measured by quantitative polymerase chain reaction and the protein expression was examined by immunohistochemistry. Serum CCL5 expression was measured by an enzyme‐linked immunosorbent assay (ELISA). C57BL/6 wild‐type (WT) and Ccl 5‐knockout ( Ccl5 −/− ) mice were utilized to conduct the diethylnitrosamine‐induced HCC model. The immune cell population was determined by flow cytometry, and peripheral serum immunoglobulin M (IgM) level was quantified by ELISA. Results CCL5 expression was low in HCC tissue and peripheral blood compared with adjacent non‐cancerous tissues or controls, and its expression was correlated with the overall survival, cancer recurrence and distant metastasis. In the HCC mouse model, liver‐to‐body weight ratio was of the Ccl5 −/− group were higher than that of the WT group. Moreover, compared with the WT mice, the number of B cells in the tumor tissue of the Ccl5 −/− mice was lower, while there were no significant differences in the other immune cell populations. Furthermore, serum IgM level of the Ccl5 −/− mice was significantly lower than that of the WT mice. Conclusion CCL5 expression is decreased in HCC tissues. CCL5 deficiency reduces B cell recruitment and decreases IgM secretion in HCC, potentially leading to tumor progression.