Alterations in CD8+ T cells, CD4+ subsets, NK cells, and immune
checkpoint expression in Mexican children newly diagnosed with pre-B
ALL, and their relationship with thrombocytopenia at diagnosis and
myelotoxicities such as neutropenia, and infections during the induction
phase of chemotherapy
Abstract
Background. Acute lymphoblastic leukemia (ALL) is the most
common childhood cancer globally. While high-income countries report
5-year survival rates exceeding 80%, low- and middle-income countries
(LMICs) face reduced rates due to treatment-related mortality (TRM).
Chemotherapy-induced myelotoxicities are significant contributors,
particularly during the induction phase. Immune parameters, including
T-helper (Th) cells, regulatory T cells (Tregs), and natural killer (NK)
cells, may influence TRM, yet their roles remain poorly understood in
LMIC settings. Methods. This prospective study evaluated 10
children newly diagnosed with pre-B ALL at a tertiary care center in
Mexico. Flow cytometry and cytokine bead arrays assessed CD8+ T cells,
CD4+ subsets, NK cells, and immune checkpoint markers at diagnosis,
during induction. Myelotoxicities and complications, including
infections and thrombocytopenia, were documented. Statistical analyses
examined associations between immune profiles, hematological
abnormalities, myelotoxicities, and clinical outcomes. Results.
CD8+ T cells increased significantly in neutropenic patients at the end
of induction (p=0.028). Reduced Th9 frequencies were observed in
patients with thrombocytopenia at diagnosis (p=0.011), while T
follicular helper (Tfh) cells decreased in those with infections at the
end of induction (p=0.032). CD56dimCD16neg/dim NK cells were elevated in
infected patients (p<0.05). Th17 and Th9 subsets co-expressing
BTLA, TIGIT, and PD-1 were increased in neutropenic patients,
highlighting immune dysregulation. Conclusions. Immune cell
profiles, particularly Th9, Tfh, and NK subsets, correlate with
hematological abnormalities and complications in children with ALL.
These findings underscore the need for further research on immune
modulation as a potential strategy to improve outcomes in LMIC contexts.