TY - JOUR
T1 - Single-cell polyfunctional proteomics of CD4 cells from patients with AML predicts responses to anti–PD-1–based therapy
AU - Abbas, Hussein A.
AU - Alaniz, Zoe
AU - Mackay, Sean
AU - Cyr, Matthew
AU - Zhou, Jing
AU - Issa, Ghayas C.
AU - Alfayez, Mansour
AU - Matthews, Jairo
AU - Kornblau, Steven M.
AU - Jabbour, Elias
AU - Garcia-Manero, Guillermo
AU - Konopleva, Marina
AU - Andreeff, Michael
AU - Daver, Naval
N1 - Publisher Copyright:
ß 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
PY - 2021/11/23
Y1 - 2021/11/23
N2 - Acute myeloid leukemia (AML) remains a difficult disease to treat disease. In a phase 2 clinical trial in patients with relapsed/refractory AML, combining the hypomethylating agent, azacitidine, with the PD-1 checkpoint inhibitor, nivolumab, demonstrated encouraging response rates (33%), median event-free, and overall survival, compared with a historical cohort of contemporary patients treated with azacitidine-based therapies, with an acceptable safety profile. Biomarkers of response are yet to be determined. In this study, we leveraged a multiplexed immune assay to assess the functional states of CD41 and CD81 cells at a single-cell level in pretherapy bone marrows in 16 patients with relapsed/refractory AML treated with azacitidine/ nivolumab. Effector CD41 but not CD81 cells had distinct polyfunctional groups and were associated with responses and better outcomes. Further evaluation of the polyfunctional strength index composition across cell types revealed that interferon-gamma (IFN-g) and tumor necrosis factor-alpha (TNF-a) were the major drivers of enhanced polyfunctionality index of pretherapy CD41 subset, whereas Granzyme B, IFN-g, MIP-1b, and TNF-a drove the nonsignificantly enhanced pretreatment Polyfunctional Strength Index of CD81 subset in the responders. Single-cell polyfunctional assays were predictive of response in AML and may have a potential role as a biomarker in the wider sphere of immunotherapy.
AB - Acute myeloid leukemia (AML) remains a difficult disease to treat disease. In a phase 2 clinical trial in patients with relapsed/refractory AML, combining the hypomethylating agent, azacitidine, with the PD-1 checkpoint inhibitor, nivolumab, demonstrated encouraging response rates (33%), median event-free, and overall survival, compared with a historical cohort of contemporary patients treated with azacitidine-based therapies, with an acceptable safety profile. Biomarkers of response are yet to be determined. In this study, we leveraged a multiplexed immune assay to assess the functional states of CD41 and CD81 cells at a single-cell level in pretherapy bone marrows in 16 patients with relapsed/refractory AML treated with azacitidine/ nivolumab. Effector CD41 but not CD81 cells had distinct polyfunctional groups and were associated with responses and better outcomes. Further evaluation of the polyfunctional strength index composition across cell types revealed that interferon-gamma (IFN-g) and tumor necrosis factor-alpha (TNF-a) were the major drivers of enhanced polyfunctionality index of pretherapy CD41 subset, whereas Granzyme B, IFN-g, MIP-1b, and TNF-a drove the nonsignificantly enhanced pretreatment Polyfunctional Strength Index of CD81 subset in the responders. Single-cell polyfunctional assays were predictive of response in AML and may have a potential role as a biomarker in the wider sphere of immunotherapy.
UR - https://www.scopus.com/pages/publications/85120399835
UR - https://www.scopus.com/pages/publications/85120399835#tab=citedBy
U2 - 10.1182/bloodadvances.2021004583
DO - 10.1182/bloodadvances.2021004583
M3 - Article
C2 - 34555853
AN - SCOPUS:85120399835
SN - 2473-9529
VL - 5
SP - 4569
EP - 4574
JO - Blood Advances
JF - Blood Advances
IS - 22
ER -