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ASH 2021: Predictive Potential of Immunosuppressive Phenotypes on Outcomes in AML

By: Joseph Fanelli
Posted: Thursday, December 23, 2021

Findings presented at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 800) suggest for many patients with acute myeloid leukemia (AML), there is an immunosuppressive phenotype at presentation of the disease mediated by inhibitory T-cell receptors through ligands expressed by the cancer cells. Timothy J. Ley, MD, of the Washington University School of Medicine, St. Louis, and colleagues found that the absence of this phenotype was strongly associated with favorable clinical outcomes for patients who received standard chemotherapy.

“The ability of CD4 T cells to be activated via the [T-cell receptor] in the presence of AML cells at presentation (which indirectly measures AML cell–mediated immunosuppression) is a novel biomarker for risk assessment that is currently not captured by any other well-recognized covariate…,” the authors concluded.

In this study, the authors utilized exome sequencing, RNA sequencing, and functional studies for an in-depth characterization of 28 patients with de novo AML who had normal karyotype cytogenetic findings and first remission more than 5 years after treatment (long first remission). These patients were compared with a cohort of 31 patients with normal-karyotype AML who relapsed within 2 years of treatment (standard first remission).

A combined analysis of single-cell RNA sequencing and flow cytometry of the AML bone marrow in patients who achieved long first remission revealed well-preserved populations of CD4 and CD8 cells that responded well to TCR-mediated activation. Conversely, patients who achieved standard first remission displayed AML marrows with a reduced number of immune cells, particularly CD4 and Th1 cells, with residual T cells expressing an exhaustion signature.

An evaluation of T-cell immune checkpoints found that LAG3 was a leading candidate for immune suppression among patients, the authors explained. In most cases of AML in patients with standard first remission, blocking the inhibitory receptor reversed AML cell–mediated T-cell suppression.

Disclosure: For full disclosures of the study authors, visit ash.com.



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