Identification and characterization of B220(+)/B220(-) subpopulations in murine Gr1(+)CD11b(+) cells during tumorigenesis

Zhang, Zhiqian1,2; Huang, Xu3; Wang, Enlin1; Huang, Yugang1; Yang, Rongcun1,4,5

2021

10.1080/2162402X.2021.1912472

ONCOIMMUNOLOGY   影响因子和分区

2162-402X

Although all murine MDSCs are defined as Gr1(+)CD11b(+), their true immunophenotype remains elusive. In this study, we found murine Gr1(+)CD11b(+) cells can be divided into two subsets: Gr1(+)CD11b(+)B220(-) and Gr1(+)CD11b(+)B220(+), especially in the spleen tissues. Unlike the dominant B220(-) subset, the B220(+) subpopulation was not induced by tumor in vivo. Moreover, Gr1(+)CD11b(+)B220(+) cells from tumor-bearing mice spleens were unable to induce arginase 1 and inducible nitric oxide synthase expression, inhibit T cell proliferation, or promote tumor growth in primary tumor site. Nevertheless, these cells suppressed tumor metastasis in vivo and reduced cancer cell motility in vitro, while Gr1(+)CD11b(+)B220(-) cells from tumor-bearing mice spleens promoted tumor metastasis and enhanced cancer cell motility. Furthermore, both the polymorphonuclear (PMN-MDSCs) and monocytic MDSCs (Mo-MDSCs) could be further divided into B220(-) and B220(+) subsets; interestingly, tumor only induced the expansion of B220(-) PMN-MDSCs and B220(-) Mo-MDSCs, but not the B220(+) counterparts. Compared with B220(-) PMN-MDSCs and B220(-) Mo-MDSCs, the Ly6G(+)Ly6C(-)CD11b(+)B220(+) and Ly6G(-)Ly6C(+)CD11b(+)B220(+) cells from tumor-bearing mice spleens exhibited a more mature phenotype without immunosuppressive activity. Additionally, IL-6 deficiency attenuated the tumor-induced accumulation of MDSCs, B220(-) MDSCs and B220(-) PMN-MDSCs but increased the percentages of Gr1(+)CD11b(+)B220(+), Ly6G(+)Ly6C(-)CD11b(+)B220(+), and Ly6G(-)Ly6C(+)CD11b(+)B220(+) cells, indicating the opposing roles of the IL-6 signaling pathway in the expansion of B220(-) MDSCs and their B220(+) counterparts. Taken together, our findings indicate that the B220(+) subset is a distinct subset of Gr1(+)CD11b(+) cells functionally different from the B220(-) subpopulation during tumorigenesis and induction of MDSCs to B220(+) cells may be helpful for cancer therapy.

MDSCs B220 tumor metastasis IL-6

SCI

英语

通讯

National Natural Science Foundation of China[31470876] ; National Natural Science Foundation of China for Youth[82002997] ; General Project of Basic Research in Shenzhen[JCYJ20190809161215057]

Oncology ; Immunology

Oncology ; Immunology

WOS:000640413100001

TAYLOR & FRANCIS INC

Web of Science

1.Nankai Univ, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China
2.Southern Univ Sci & Technol, Sch Med, Shenzhen, Guangdong, Peoples R China
3.Harbin Med Univ, Canc Hosp, Dept Radiat Oncol, Harbin, Heilongjiang, Peoples R China
4.Nankai Univ, Minist Educ, Key Lab Bioact Mat, Tianjin, Peoples R China
5.Nankai Univ, Sch Med, Dept Immunol, Tianjin, Peoples R China

Zhang, Zhiqian,Huang, Xu,Wang, Enlin,et al. Identification and characterization of B220(+)/B220(-) subpopulations in murine Gr1(+)CD11b(+) cells during tumorigenesis[J]. ONCOIMMUNOLOGY,2021,10(1).

Zhang, Zhiqian,Huang, Xu,Wang, Enlin,Huang, Yugang,&Yang, Rongcun.(2021).Identification and characterization of B220(+)/B220(-) subpopulations in murine Gr1(+)CD11b(+) cells during tumorigenesis.ONCOIMMUNOLOGY,10(1).

Zhang, Zhiqian,et al."Identification and characterization of B220(+)/B220(-) subpopulations in murine Gr1(+)CD11b(+) cells during tumorigenesis".ONCOIMMUNOLOGY 10.1(2021).