# Program control of CD8+ T cell response to tumors and tumor memory

> **NIH CA R01** · H. LEE MOFFITT CANCER CTR & RES INST · 2026 · $549,460

## Abstract

Abstract
CD8+ tumor infiltrating lymphocytes (TILs) are not only critical for the anti-tumor immune response in solid
tumors, but also in the success of adoptive cell therapies and in immune check point blockade (ICB) treatments.
CD8+ TILs have been shown to be heterogeneous, and in time to progress to a terminally exhausted state, with
no ability to respond, and resistant to reprograming by ICB. It remains of critical importance to understand the
biology, transcriptional programs and epigenetic control of the progression of the precursors, which have high
functional potential and stemness, to the terminally exhausted CD8+ TILs.
Cells with characteristics of memory have been identified in tumors and their presence is associated with
a positive outcome. Recently a memory CD8+ T cell population has been identified, located predominantly in
tumor draining LNs and showing an efficient antitumor response upon recall. However, little it is known about
tumor memory cells, their response, transcriptional and epigenetic control, as well as their failure in
recurrent tumors associated with relapse.
Our preliminary data show that ablation of the transcription factor BCL11B in TILs unleashes stemness at the
same time with the effector programs, but restricts exhaustion, providing TILs with increased ability to promote
a more efficient anti-tumor response compared to WT counterparts. In addition, depletion of BCL11B in TILs
from a patient who did not respond to TIL adoptive cell therapy, improved their cytolytic activity. We hypothesize
that BCL11B plays a central role in controlling essential programs of TILs, including stemness, effector and
exhaustion. Our preliminary data also show BCL11B KO tumor memory cells outperform WT memory
cells in a recall response to tumors.
Using scRNAseq and genome-wide histone marks analyses we will establish the programs and epigenomic
landscape controlled by BCL11B in mouse TILs. In addition, we will investigate the programs and the epigenomes

## Key facts

- **NIH application ID:** 11392228
- **Project number:** 5R01CA293755-02
- **Recipient organization:** H. LEE MOFFITT CANCER CTR & RES INST
- **Principal Investigator:** Dorina  Avram; Timothy Isham Shaw
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** CA
- **Fiscal year:** 2026
- **Award amount:** $549,460
- **Award type:** 5
- **Project period:** 2025-08-13T00:00:00 → 2030-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11392228

## Citation

> US National Institutes of Health, RePORTER application 11392228, Program control of CD8+ T cell response to tumors and tumor memory (5R01CA293755-02). Retrieved via AI Analytics 2026-05-19 from https://api.ai-analytics.org/grant/nih/11392228. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*