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// Chuanbao Zhang 1, * , Jiye Li 1, 2, 3, * , Haoyuan Wang 4 , Sonya Wei Song 1, 2, 3 1 Beijing Neurosurgical Institute, Capital Medical University, TiantanXili, Dongcheng District, Beijing 100050, China 2 Beijing Institute for Brain Disorders, Youanmen, Beijing, 100069, China 3 Center for Brain Disorders Research, Capital Medical University, Youanmen, Beijing, 100069, China 4 Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China * These authors contributed equally to this work Correspondence to: Sonya Wei Song, email: sonyasongbj2016@163.com , sonyasong@ccmu.edu.cn Keywords: immune system, tumor-infiltrating B cells, prognosis, biomarker, glioma Received: April 11, 2016 Accepted: September 27, 2016 Published: October 12, 2016 ABSTRACT High grade gliomas contribute to most brain tumor mortality. A few studies reported that the immune system affected glioma development, and immune biomarkers helped understand the disease and formulate effective immunotherapy for patients. Currently, no B lymphocyte-based prognostic signature was reported in gliomas. By applying 78 B cell lineage-specific genes, we conducted a whole-genome gene expression analysis in 782 high grade gliomas derived from three independent datasets by Cox regression analysis and risk score method for signature identification, and then used Gene Ontology, Gene Set Enrichment Analysis, and other statistical methods for functional annotations of the signature-defined differences. We developed a five B cell-associated gene signature for prognosis of high grade glioma patients, which is independent of clinicopathological and genetic features. The signature identified high risk patients suitable for chemoradiotherapy, whereas low risk patients should rule out chemotherapy with radiotherapy only. We found that tumors of TCGA Mesenchymal subtype and wild type IDH1 were preferentially stratified to the high risk group, which bore strong immunosuppressive microenvironment, while tumors of TCGA Proneural subtype and mutated IDH1 were significantly accumulated to the low risk group, which exhibited less immunosuppressive state. The five B cell-associated gene signature predicts poor survival of high risk patients bearing strong immunosuppression and helps select optimal therapeutic regimens for glioma patients.

Accumulating evidence indicated that B lymphocytes exerted complex functions in tumor immunity. On the one hand, B lymphocytes can inhibit tumor development through antibody generation, antigen presentation, tumor tissue interaction, and direct killing. On the other hand, B lymphocytes have tumor-promoting functions. A typical type of B lymphocytes, termed regulatory B cells, is confirmed to attenuate immune response in a tumor environment. In this paper, we summarize the current understanding of B-cell functions in tumor immunology, which may shed light on potential therapeutic strategies against cancer.