ArticleJournal for immunotherapy of cancer2022
Association of race/ethnicity with innate immune tumor microenvironment of children with B-acute lymphoblastic leukemia.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundBlack 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.
methodsWe 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.
resultsRace/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.
conclusionThere 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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