Session: 617. Acute Myeloid Leukemias: Biomarkers, Molecular Markers and Minimal Residual Disease in Diagnosis and Prognosis: Poster I
Hematology Disease Topics & Pathways:
Research, Acute Myeloid Malignancies, AML, Combination therapy, bioinformatics, Diseases, Therapies, computational biology, Myeloid Malignancies, Technology and Procedures
At the pseudobulk level, we observed baseline activity in the chemoattractive, effector, and regulatory functional groups was higher in both PB and BM CD8 cells compared to CD4 cells (Fig 1A), suggesting increased polyfunctionality in CD8 T cells prior to treatment. Analysis comparing pretreatment and post-ICB polyfunctionality revealed similar response patterns in CD4 and CD8 T cells in both the PB and BM spaces. Interestingly, CD4 T cells exhibited increased polyfunctional activity post-ICB in both PB and BM as compared to CD8 T cells. These findings point to an unexpected contribution of CD4 T cells with ICB therapy in AML.
We employed an unbiased, unsupervised neighborhood analysis which leveraged the nearest cellular neighbor based on the log fold-change in secreted proteins between samples from distinct timepoints to reveal post-ICB CD4 and CD8 T cells aggregated into distinct cellular neighborhoods (Fig 1B). Both CD4 and CD8 analysis revealed distinct groups highlighting one group containing pre-ICB cells, and another group containing pre- and post-ICB cells. This suggests that T cell functionality is predetermined prior to ICB therapy. Comparative analysis at the single-cell level further identified higher expression of chemoattractive, inflammatory, regulatory, and stimulatory polyfunctional groups in non-responders (NR) in the BM for both CD4 and CD8 T cells, and higher expression of the chemoattractive group in NRs in the PB for CD4 cells. This suggests that BM polyfunctionality may be more critical in terms of ICB response.
This study provides a novel single-cell functional analysis of T cells from both PB and BM compartments in RelRef AML patients treated with ICB. Our findings suggest the functional state of T cells in the circulating state and residence within the leukemia microenvironment are not equivalent and that there are dynamic changes of T cell functionality with ICB which has broad implications for correlative sample analysis in the ICB setting.
Disclosures: Alfayez: Amgen: Honoraria; Johnson & Johnson: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Biologics: Consultancy, Honoraria; Abbvie: Research Funding; Astellas: Honoraria; AstraZeneca: Honoraria. Daver: AROG: Consultancy; Daiichi Sankyo: Consultancy, Research Funding; FATE: Research Funding; Trovagene: Research Funding; Hanmi: Research Funding; Novimmune: Research Funding; Glycomimetics: Research Funding; Genentech: Consultancy, Research Funding; Jazz: Consultancy; Pfizer: Consultancy, Research Funding; Syndax: Consultancy; Novartis: Consultancy; Shattuck Labs: Consultancy; Celgene: Consultancy; ImmunoGen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Trillium: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Agios: Consultancy; Servier: Consultancy, Research Funding; Kite, a Gilead company: Consultancy, Research Funding; Kronos Bio: Research Funding. Abbas: Molecular Partners: Consultancy; Illumina: Other: In-kind products ; Genentech: Research Funding; Gilead: Research Funding.