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Association of race/ethnicity with innate immune tumor microenvironment of children with B-acute lymphoblastic
Julie R Gilbert1, Himalee S Sabnis1, Roman Radzievski2
1Aflac Cancer and Blood Disprders Center, Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia, U.S.A.
Insights
Racial disparities exist in the immune cells of children with B-acute lymphoblastic leukemia (B-ALL). Understanding these differences in innate immunity is crucial for improving outcomes in minority children undergoing immunotherapy.
Area of Science:
- Immunology
- Pediatric Oncology
- Hematology
Background:
- Black and Hispanic children with B-acute lymphoblastic leukemia (B-ALL) have poorer outcomes than non-Hispanic white (NHW) children.
- Immune-based therapies are transforming B-ALL treatment, but the impact of race/ethnicity on the immune microenvironment is understudied.
- Minority children are under-represented in studies investigating immune alterations in B-ALL.
Purpose of the Study:
- To investigate race/ethnicity-associated differences in the innate immune microenvironment of children with newly diagnosed B-ALL.
- To identify specific immune cell populations and their alterations in relation to racial/ethnic background.
Main Methods:
- High-dimensional mass cytometry analysis of bone marrow samples from 85 children with newly diagnosed B-ALL (Hispanic, Black, NHW).
- Utilized 40- and 38-marker panels to comprehensively analyze immune cell populations.
Main Results:
- Significant race/ethnicity-based differences were observed, particularly in the innate immune compartment.
- Hispanic patients showed increased mature CD57+T-bet+DR+ NK cells, especially within standard-risk B-ALL.
- Hispanic and Black children exhibited distinct myeloid cell alterations, including increased non-classical activated HLA-DR+CD16+ myeloid cells, and altered PD-L1 expression on myeloid cells.
Conclusions:
- Substantial race/ethnicity-based differences in innate immune cells of children with B-ALL exist.
- These findings highlight the need for increased minority enrollment in immunotherapy trials for B-ALL.
- Addressing these immune disparities may improve treatment outcomes for minority children with B-ALL.
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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