期刊
BLOOD ADVANCES
卷 5, 期 22, 页码 4569-4574出版社
ELSEVIER
DOI: 10.1182/bloodadvances.2021004583
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类别
资金
- MD Anderson Cancer Centre Support Grant [CA016672]
- MD Anderson Cancer Center Leukemia SPORE [CA100632]
- Charif Souki Cancer Research Fund
- Dick Clark Immunotherapy Fund
In patients with relapsed/refractory AML, the study showed that CD4(+) cells with distinct polyfunctional groups were associated with responses and better outcomes, potentially serving as a biomarker for immunotherapy in AML. Further evaluation revealed specific cytokines driving the enhanced polyfunctionality index in CD4(+) and CD8(+) subsets of responders. Single-cell polyfunctional assays were predictive of treatment response in AML, suggesting a potential role in immunotherapy biomarker discovery.
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 CD4(+) and CD8(+) cells at a single-cell level in pretherapy bone marrows in 16 patients with relapsed/refractory AML treated with azacitidine/nivolumab. Effector CD4(+ )but not CD8(+) 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-gamma) and tumor necrosis factor-alpha (TNF-alpha) were the major drivers of enhanced polyfunctionality index of pretherapy CD4(+) subset, whereas Granzyme B, IFN-gamma, MIP-1b, and TNF-alpha drove the nonsignificantly enhanced pretreatment Polyfunctional Strength Index of CD8(+ )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.
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