Immune Characteristics of Chinese Diffuse Large B-Cell Lymphoma Patients: Implications for Cancer Immunotherapies
Peng-peng Xu,
Chun Sun,
Xu Cao,
Xia Zhao,
Hang-jun Dai,
Shan Lu,
Jian-jun Guo,
Shi-jing Fu,
Yu-xia Liu,
Su-chun Li,
Meng Chen,
Ron McCord,
Jeff Venstrom,
Edith Szafer-Glusman,
Elizabeth Punnoose,
Astrid Kiermaier,
Gang Cheng,
Wei-li Zhao
Affiliations
Peng-peng Xu
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Chun Sun
Oncology Biomarker Development, Genentech Inc., Shanghai, China
Xu Cao
Oncology Biomarker Development, Genentech Inc., Shanghai, China
Xia Zhao
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Hang-jun Dai
Roche Product Development in Asia Pacific, Roche (China) Holding, Ltd., Shanghai, China
Shan Lu
Oncology Biomarker Development, Genentech Inc., South San Francisco, CA, USA
Jian-jun Guo
Oncology Biomarker Development, Genentech Inc., Shanghai, China
Shi-jing Fu
Oncology Biomarker Development, Genentech Inc., Shanghai, China
Yu-xia Liu
Oncology Biomarker Development, Genentech Inc., Shanghai, China
Su-chun Li
Roche Product Development in Asia Pacific, Roche (China) Holding, Ltd., Shanghai, China
Meng Chen
Roche Product Development in Asia Pacific, Roche (China) Holding, Ltd., Shanghai, China
Ron McCord
Oncology Biomarker Development, Genentech Inc., South San Francisco, CA, USA
Jeff Venstrom
Oncology Biomarker Development, Genentech Inc., South San Francisco, CA, USA
Edith Szafer-Glusman
Oncology Biomarker Development, Genentech Inc., South San Francisco, CA, USA
Elizabeth Punnoose
Oncology Biomarker Development, Genentech Inc., South San Francisco, CA, USA
Oncology Biomarker Development, Genentech Inc., Shanghai, China; Correspondence to: G. Cheng, 1100 Long-dong Avenue, Shanghai 201203, China.
Wei-li Zhao
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Correspondence to: W. Zhao, 197 Rui-jin Er Road, Shanghai 200025, China.
Immunotherapeutic agents have demonstrated encouraging signs of clinical utility in non-Hodgkin lymphoma. The goal of this study is to analyze the immune characteristics of Chinese patients with diffuse large B-cell lymphoma (DLBCL) to inform the development of immunotherapies in this patient population. Tumor samples from 211 DLBCL patients were analyzed for cell of origin (COO) and immune characteristics using the NanoString platform as well as MYC protein expression through immunohistochemistry. Lower incidence of the germinal center B-cell (GCB) subtype (93/211, 44.1%) was observed in this cohort. Compared to the GCB subtype, the activated B-cell (ABC) subtype was associated with significantly increased expression of multiple pro-inflammatory gene signatures and decreased expression of anti-inflammatory gene signatures. Instead of affecting the pro-inflammatory genes, MYC protein overexpression showed a negative correlation with the expression of T-cell receptor (TCR) and T regulatory genes as well as the OX40 gene. Regardless of COO, higher PD-L1 or IDO1 gene expression correlated with increased expression of T effector and Interferon-γ gene signatures while the expression of multiple oncogenes including ACTR3B, ERBB2, AKT2 and SMARCD1 was down-regulated. Our findings may thus be helpful in guiding further development of immunotherapies for the different subsets of Chinese DLBCL patients. Keywords: DLBCL, Cell of origin, Immune characteristics, Immunotherapy