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

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...

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Autores principales: Gilbert, Julie R, Sabnis, Himalee S, Radzievski, Roman, Doxie, Deon B, DeRyckere, Deborah, Castellino, Sharon M, Dhodapkar, Kavita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204408/
https://www.ncbi.nlm.nih.gov/pubmed/35710294
http://dx.doi.org/10.1136/jitc-2022-004774
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author Gilbert, Julie R
Sabnis, Himalee S
Radzievski, Roman
Doxie, Deon B
DeRyckere, Deborah
Castellino, Sharon M
Dhodapkar, Kavita
author_facet Gilbert, Julie R
Sabnis, Himalee S
Radzievski, Roman
Doxie, Deon B
DeRyckere, Deborah
Castellino, Sharon M
Dhodapkar, Kavita
author_sort Gilbert, Julie R
collection PubMed
description 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.
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spelling pubmed-92044082022-06-29 Association of race/ethnicity with innate immune tumor microenvironment of children with B-acute lymphoblastic leukemia Gilbert, Julie R Sabnis, Himalee S Radzievski, Roman Doxie, Deon B DeRyckere, Deborah Castellino, Sharon M Dhodapkar, Kavita J Immunother Cancer Immunotherapy Biomarkers 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. BMJ Publishing Group 2022-06-16 /pmc/articles/PMC9204408/ /pubmed/35710294 http://dx.doi.org/10.1136/jitc-2022-004774 Text en © 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. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Immunotherapy Biomarkers
Gilbert, Julie R
Sabnis, Himalee S
Radzievski, Roman
Doxie, Deon B
DeRyckere, Deborah
Castellino, Sharon M
Dhodapkar, Kavita
Association of race/ethnicity with innate immune tumor microenvironment of children with B-acute lymphoblastic leukemia
title Association of race/ethnicity with innate immune tumor microenvironment of children with B-acute lymphoblastic leukemia
title_full Association of race/ethnicity with innate immune tumor microenvironment of children with B-acute lymphoblastic leukemia
title_fullStr Association of race/ethnicity with innate immune tumor microenvironment of children with B-acute lymphoblastic leukemia
title_full_unstemmed Association of race/ethnicity with innate immune tumor microenvironment of children with B-acute lymphoblastic leukemia
title_short Association of race/ethnicity with innate immune tumor microenvironment of children with B-acute lymphoblastic leukemia
title_sort association of race/ethnicity with innate immune tumor microenvironment of children with b-acute lymphoblastic leukemia
topic Immunotherapy Biomarkers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204408/
https://www.ncbi.nlm.nih.gov/pubmed/35710294
http://dx.doi.org/10.1136/jitc-2022-004774
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