# Mechanisms of immune evasion in T-cell acute lymphoblastic leukemia and its therapeutic implications

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $238,971

## Abstract

Project Summary
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic malignancy in children and young
adults that frequently becomes treatment-refractory and relapses. Although cure rates have improved with
intensified multi-agent chemotherapy, relapsed or treatment refractory disease remains very difficult to treat.
Therefore, there is a great medical need for identifying novel vulnerabilities and therapeutic approaches.
Targeting of the immunosuppressive tumor microenvironment has led to promising results in many solid tumors.
Yet, comprehensive studies of the T-ALL microenvironment, which are necessary to characterize
leukemia/immune cell interactions and identify therapeutic vulnerabilities, have not been performed. Using single
cell sequencing technologies of T-ALL blasts and their microenvironmental cells, we have generated preliminary
data suggesting a novel role of immune evasion in T-ALL with the potential to incorporate immunotherapy
approaches into current treatment regimens to overcome T-cell exhaustion. This proposal seeks to define novel
mechanisms of immune evasion in T-ALL and develop means for their therapeutic targeting. We will define
mechanisms of CD8+ T-cell dysfunction by combining RNA-Seq, immune repertoire and protein analysis in single
leukemia and microenvironmental cells in primary T-ALL patient samples and determine the necessary and
sufficient exhaustion receptor/ligands through functional perturbation in in vitro and in vivo models of T-ALL (aim
1); We will study epigenetic and transcriptional mechanisms that regulate immune evasion in T-ALL and develop
novel strategies to target T-cell dysfunction in pediatric leukemias by perturbing the epigenetic machinery (aim
2). Successful completion of this proposal is expected to uncover novel mechanisms of immune evasion in T-
ALL and will lead to development of innovative therapeutic strategies for targeting T-cell exhaustion in the
immune microenvironment in patients with high-risk T-ALL. The principles described in T-ALL will have a
significant impact on a wide variety of malignancies.

## Key facts

- **NIH application ID:** 11229540
- **Project number:** 7R01CA249185-05
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Birgit Knoechel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $238,971
- **Award type:** 7
- **Project period:** 2021-08-24 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11229540

## Citation

> US National Institutes of Health, RePORTER application 11229540, Mechanisms of immune evasion in T-cell acute lymphoblastic leukemia and its therapeutic implications (7R01CA249185-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11229540. Licensed CC0.

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