MAY 20, 2020 11:45 AM EDT | APAC MAY 21, 2020 2:45 PM CST

Immune Infiltration Correlates of TP53 Mutational Status in Acute Myeloid Leukemia

Speaker

Abstract

Tumor phenotypes are dictated not only by the neoplastic cell component, but also by the tumor microenvironment (TME), which is inherently immuno-suppressive, is equipped to hamper effector T-cell function and includes immune and inflammatory cells, soluble mediators such as interferon (IFN)-g and extracellular matrix components. Acute myeloid leukemia (AML) is characterized by clonal expansion of poorly differentiated myeloid precursors, resulting in impaired hematopoiesis and often bone marrow (BM) failure. TP53 mutations occur in 8-10% of de novo AML and are associated with poor prognostic features. The development and delivery of new therapeutic strategies for high-risk AML, including immunotherapy, therefore remains a priority.

Our multi-institutional study was undertaken to characterize the immune ecosystem of non-promyelocytic AML with TP53 mutations using he nCounter™ system (NanoString Technologies Inc., Seattle, WA), with the ultimate goal to implement new immunotherapy agents for patients with specific immunologic subtypes of AML.

We detected high T-cell infiltration and high expression of immune checkpoints and IFN-g signaling molecules in patients with TP53 mutated AML compared with AML subgroups with other risk-defining molecular lesions. We also computed an experimentally derived, TP53-related immune gene signature which stratified survival in a broad cohort of TCGA AML cases. Finally, our correlative analysis in patients with relapsed/refractory AML treated with flotetuzumab, an investigational immunotherapy, showed efficacy in individuals with altered TP53 status and identified immune gene signature that support the prediction of therapeutic responses.

In conclusion, our study has identified unique immunological profiles in patients with TP53 mutated AML. From a clinical standpoint, ‘immune enriched’ AMLs might be amenable to immunotherapy approaches with T-cell engagers.


Show Resources
You May Also Like
SEP 14, 2021 7:00 AM PDT
C.E. CREDITS
SEP 14, 2021 7:00 AM PDT
Date: September 14, 2021 Time: 7am PDT, 10am EDT, 4pm CEST A conventional thermal cycler has long been a commodity product in the lab and end-point PCR techniques can be completed almost wit...
JUN 09, 2021 7:00 AM PDT
C.E. CREDITS
JUN 09, 2021 7:00 AM PDT
Date: June 9, 2021 Time: 09 June 2021, 7am PDT, 10am EDT, 4pm CEST cells with dramatic implications on the validity of past cell culture related research. The fact that at least 509 cell lin...
NOV 09, 2021 11:00 AM PST
C.E. CREDITS
NOV 09, 2021 11:00 AM PST
Date: November 09, 2021 Time: 11:00am (PDT), 02:00pm (EDT) Clinical translation of human pluripotent stem cells (hPSCs) requires advanced strategies that ensure safe and robust long-term gro...
JUN 03, 2021 12:00 PM CST
JUN 03, 2021 12:00 PM CST
DATE: June 3, 2021 TIME: 12:00pm SGT This webinar is a virtual event that focuses on utilizing the Gibco CTS Rotea System for Cell and Gene Therapy...
DEC 01, 2021 7:00 AM PST
C.E. CREDITS
DEC 01, 2021 7:00 AM PST
Date: December 01, 2021 Time: 7:00am (PST), 10:00am (EST) In the era of immuno-oncology, there is a growing need for the identification of new biomarkers predictive for sensitivity to anti-P...
JUL 15, 2021 9:00 AM PDT
JUL 15, 2021 9:00 AM PDT
Date: July 15, 2021 Time: 9:00am (PDT), 12:00pm (EDT) The Pisces workflow robust, easy-to-use, end-to-end multi-omics solution for highly multiplexed targeted Spatial RNA analysis. VeranomeB...
Loading Comments...
Show Resources