Association of race/ethnicity with innate immune tumor microenvironment of children with B-acute lymphoblastic leukemia

• Type of Material: Article
• Authors: Julie R Gilbert, Emory University; Himalee Sabnis, Emory University; Roman Radzievski, Emory University; Deon B Doxie, Emory University; Deborah DeRyckere, Emory University; Sharon Castellino, Emory University; Kavita Dhodapkar, Emory University
• Language: English
• Date: 2022-06-01
• Publisher: BMJ PUBLISHING GROUP
• Publication Version: Final Published Version
• Copyright Statement: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/jitc-2022-004774
• Title of Journal or Parent Work: JOURNAL FOR IMMUNOTHERAPY OF CANCER
• Volume: 10
• Issue: 6
• Grant/Funding Information: This study was funded by Cancer Center and Aflac (P30CA138292).
• Keywords: Oncology; Immunology; RISK; Life Sciences & Biomedicine; SURVIVAL; Tumor Microenvironment; Science & Technology; SOCIOECONOMIC-STATUS; POLYMORPHISMS; Hematologic Neoplasms
• Research Categories: Health Sciences, Oncology

Abstract

Background Black and Hispanic children with B-acute lymphoblastic leukemia (B-ALL) experience worse outcomes compared with their non-Hispanic white (NHW) counterparts. Immune-based approaches have begun to transform the therapeutic landscape in children with B-ALL. Recent studies identified several alterations in both innate and adaptive immune cells in children with B-ALL that may impact disease risk and outcome. However, the impact of racial/ethnic background on immune microenvironment is less studied, as children of minorities background have to date been severely under-represented in such studies. Methods We performed high-dimensional analysis of bone marrow from 85 children with newly diagnosed B-ALL (Hispanic=29, black=18, NHW=38) using mass cytometry with 40 and 38-marker panels. Results Race/ethnicity-associated differences were most prominent in the innate immune compartment. Hispanic patients had significantly increased proportion of distinct mature CD57 +T-bet+DR+ NK cells compared with other cohorts. These differences were most apparent within standard risk (SR) patients with Hispanic SR patients having greater numbers of CD57 +NK cells compared with other cohorts (43% vs 26% p=0.0049). Hispanic and Black children also had distinct alterations in myeloid cells, with a significant increase in a population of non-classical activated HLA-DR +CD16+myeloid cells, previously implicated in disease progression, compared with NHW counterparts. Racial background also correlated with altered expression of inhibitory checkpoint PD-L1 on myeloid cells. Conclusion There are surprisingly substantial race/ethnicity-based differences in innate immune cells of children with newly diagnosed B-ALL. These differences urge the need to enhance accrual of children from minorities background in immunetherapy trials and may impact their outcome following such therapy.