Source: School of Life Sciences
Written by: School of Life Sciences
Edited by: Wang Dongmei

Recently, a research article entitled “PD-1^High Identifies a Novel Regulatory B Cell Population in Human Hepatoma that Promotes Disease Progression” has been published online in Cancer Discovery, one of the top-notch journals in oncology (Impact Factor: 19.453). This study led by Prof. Dong-Ming Kuang from School of Life Sciences at Sun Yat-sen University unveiled a group of previously unrecognized tumor-promoting B cells and investigated the phenotype, mechanisms of induction, biological function, and clinical relevance of these cells in human hepatocellular carcinoma (HCC)^[1].

B cells function as the major effectors of humoral immunity by secreting antibodies, and they consistently represent important and abundant cellular components in tumors. But the subset composition and the biological roles of B cells in human cancer are poorly understood. Prof. Kuang and his team have been collaborating with Prof. Xiang-Ming Lao from SYSU Cancer Center on B cell research since 2010, and they have previously demonstrated the crucial mechanisms of B cell infiltration and plasma cell maturation in HCC tumors^[2]. Their newly published article in Cancer Discovery focuses on a specific population of protumorigenic B cells that expressed high levels of PD-1 molecules and displayed potent regulatory functions. Along with the identification and phenotypic characterization, the article sheds light on how these PD-1^high B cells were generated and how they suppressed anti-tumor immunity and affected disease progression. The major findings are as follows: 1) PD-1^high B cells constituted approximately 10% of all B cells in advanced stage HCC and they correlated with patients’ early recurrence; 2) Bcl-6 upregulation mediated by activation of pattern recognition receptor TLR4 was vital for PD-1high B cell generation induced by tumor environment, which could be abolished by IL-4-elicited STAT6 phosphorylation; 3) PD-1^high B cells, upon triggering by PD-L1 signals, operated via IL-10-dependent pathways to cause T cell dysfunction and contributed to cancer progression.

As the clinical application of monoclonal antibodies increases, the humoral facet of B cell immunity receives increasing attention. However, Prof. Kuang and his team showed that B cells could also engage in cellular immunity in which they exerted negative regulation on T cell anti-tumor activity in human HCC. This work significantly adds to the present knowledge of B cell immunity and to the diversified actions of the primary inhibitory axis PD-1–PD-L1 in cancer microenvironments. The obscure complexity of B cells in tumor immunology calls for more studies and investigations, based on which new therapeutic approaches may emerge.

References (*Corresponding author)
【1】 Xiao X, Lao XM, Chen MM, Liu RX, Wei Y, Ouyang FZ, Chen DP, Zhao XY, Zhao Q, Li XF, Liu CL, Zheng L, Kuang DM*. 2016. PD-1^High Identifies a Novel Regulatory B Cell Population in Human Hepatoma that Promotes Disease Progression. Cancer Discov. Online First on February 29, 2016; DOI: 10.1158/2159-8290.CD-15-1408.
http://cancerdiscovery.aacrjournals.org/content/early/2016/03/02/2159-8290.CD-15-1408.1

【2】 Liu RX, Wei Y, Zeng QH, Chan KW, Xiao X, Zhao XY, Chen MM, Ouyang FZ, Chen DP, Zheng L, Lao XM, Kuang DM*. 2015. Chemokine (C-X-C motif) receptor 3-positive B cells link interleukin-17 inflammation to protumorigenic macrophage polarization in human hepatocellular carcinoma. Hepatology. 62:1779–1790.
http://onlinelibrary.wiley.com/doi/10.1002/hep.28020/full