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Schaafsma et al. J Cancer Metastasis Treat 2021;7:34               Journal of Cancer
               DOI: 10.20517/2394-4722.2021.72
                                                                       Metastasis and Treatment




               Original Article                                                              Open Access



               B cell infiltration is highly associated with prognosis
               and an immune-infiltrated tumor microenvironment

               in neuroblastoma

                                                 3
                               1,2
               Evelien Schaafsma , Chongming Jiang , Chao Cheng 2,3,4,5
               1
                Department of Molecular and Systems Biology, Dartmouth College, Hanover, NH 03755, USA.
               2
                Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
               3
                Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
               4
                Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
               5
                The Institute for Clinical and Translational Research, Baylor College of Medicine, Houston TX, 77030, USA.
               Correspondence to: Chao Cheng, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030,
               USA. E-mail: chao.cheng@bcm.edu
               How to cite this article: Schaafsma E, Jiang C, Cheng C. B cell infiltration is highly associated with prognosis and an immune-
               infiltrated tumor microenvironment in neuroblastoma. J Cancer Metastasis Treat 2021;7:34.
               https://dx.doi.org/10.20517/2394-4722.2021.72

               Received: 19 Mar 2021  First Decision: 13 May 2021  Revised: 18 May 2021  Accepted: 2 Jun 2021   First online: 6 Jun 2021

               Academic Editor: Steven Fiering Copy Editor: Yue-Yue Zhang Production Editor: Yue-Yue Zhang

               Abstract
               Aim: Neuroblastoma is the most common extracranial solid tumor in children. Recent advances in immunotherapy
               Approaches, including in neuroblastoma, have shown the important role of the immune system in mounting an
               effective anti-tumor response. In this study, we aimed to provide a comprehensive investigation of immune cell
               infiltration in neuroblastoma utilizing a large number of gene expression datasets.

               Methods: We inferred immune cell infiltration using an established immune inference method and evaluated the
               association between immune cell abundance and patient prognosis as well as common chromosomal abnormalities
               found in neuroblastoma. In addition, we evaluated co-infiltration patterns among distinct immune cell types.

               Results: The infiltration of naïve B cells, NK cells, and CD8+ T cells was associated with improved patient
               prognosis. Naïve B cells were the most consistent indicator of prognosis and associated with an active immune
               tumor microenvironment. Patients with high B cell infiltration showed high co-infiltration of other immune cell
               types and the enrichment of immune-related pathways. The presence of high B cell infiltration was associated with
               both recurrence-free and overall survival, even after adjusting for clinical variables.






                           © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
                           International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
                           adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
               long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
               indicate if changes were made.

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