CD20highCD138low tumor-infiltrating lymphocytes predominantly related to cytokine‒cytokine receptor interactions are associated with favorable outcomes in neuroblastoma patients
Liang-Jun Qin,
Hui Xu,
Li-Ping Li,
Shu-Hua Li,
Shuo-Yu Xu,
Kai Chen,
Tianyou Yang,
Feng-Hua Wang,
Liandong Zuo,
Liang Zeng,
Hai-Yun Wang
Affiliations
Liang-Jun Qin
Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children's Medical Center for South Central Region, Guangzhou, 510623, China
Hui Xu
Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children's Medical Center for South Central Region, Guangzhou, 510623, China
Li-Ping Li
Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children's Medical Center for South Central Region, Guangzhou, 510623, China
Shu-Hua Li
Department of Paediatric Outpatient, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children's Medical Center for South Central Region, Guangzhou, 510623, China
Shuo-Yu Xu
Bio-totem Pte. Ltd., Foshan, 528231, China; Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
Kai Chen
Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children's Medical Center for South Central Region, Guangzhou, 510623, China
Tianyou Yang
Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children's Medical Center for South Central Region, Guangzhou, 510623, China
Feng-Hua Wang
Department of Thoracic Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children's Medical Center for South Central Region, Guangzhou, 510623, China
Liandong Zuo
Department of Andrology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China
Liang Zeng
Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children's Medical Center for South Central Region, Guangzhou, 510623, China; Corresponding author. Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children's Medical Center for South Central Region, No. 9 Jinsui Road, Guangzhou, 510623, China.
Hai-Yun Wang
Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children's Medical Center for South Central Region, Guangzhou, 510623, China; Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children's Medical Center for South Central Region, Guangzhou, 510623, China; Corresponding author. Department of Pathology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children's Medical Center for South Central Region, No. 9 Jinsui Road, Guangzhou, 510623, China.
Recent advances have revealed that the role of the immune system is prominent in the antitumor response. In the present study, it is aimed to provide an expression profile of tumor-infiltrating lymphocytes (TILs), including mature B cells, plasma cells, and their clinical relevance in neuroblastoma. The expression of CD20 and CD138 was analyzed in the Cangelosi786 dataset (n = 769) as a training dataset and in our cohort (n = 120) as a validation cohort. CD20 high expression was positively associated with favorable overall survival (OS) and event-free survival (EFS) (OS: P < 0.001; EFS: P < 0.001) in the training dataset, whereas CD138 high expression was associated with poor OS and EFS (OS: P < 0.001; EFS: P < 0.001) in both the training and validation datasets. Accordingly, a combined pattern of CD20 and CD138 expression was developed, whereby neuroblastoma patients with CD20highCD138low expression had a consistently favorable OS and EFS compared with those with CD20lowCD138high expression in both the training and validation cohorts (P < 0.0001 and P < 0.01, respectively). Examination of potential molecular functions revealed that signaling pathways, including cytokine‒cytokine receptor interactions, chemokine, and the NF-kappa B signaling pathways, were involved. Differentially expressed genes, such as BMP7, IL7R, BIRC3, CCR7, CXCR5, CCL21, and CCL19, predominantly play important roles in predicting the survival of neuroblastoma patients. Our study proposes that a new combination of CD20 and CD138 signatures is associated with neuroblastoma patient survival. The related signaling pathways reflect the close associations among the number of TILs, cytokine abundance and patient outcomes and provide therapeutic insights into neuroblastoma.
