# Understanding and Overcoming T cell Immunosuppression in Glioblastoma

> **NIH NIH P01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $2,680,832

## Abstract

Abstract
Glioblastoma (GBM) remains a formidable cancer to treat with only anecdotal examples of long-term survivors.
Recently, immunotherapy has seen multiple successes against various types of cancer, but several recent
clinical trials of this modality in GBM have not been successful. It is evident that two inter-related factors in the
complex immunobiology of GBM have thwarted therapeutic efficacy: the existence of multiple
immunosuppressive mechanisms and the significant lymphodepletion in the GBM microenvironment. The
overarching goal of the Program Project is to address the problem of insufficient T cell activation and marked T
cell attenuation in the GBM microenvironment. We will test the overall hypothesis that promotion of CD8+
and CD4+ T cell functionality can overcome the highly immunosuppressive mechanisms of GBM. A
corollary to this hypothesis is that preclinical and clinical trials of immunotherapy combinations will provide
an effective approach to GBM treatment. We have assembled a highly interactive and interdisciplinary team
of 11 investigators in 4 highly integrated Research Projects, supported by 4 Cores. This team (some of whom
have been working together for more than two decades) brings deep expertise in immunobiology, neuro-
oncology, clinical trials, genomics and computational analyses to mechanistically study these two critical factors.
We plan to study how immune checkpoint blockade can be combined with other T cell activating
immunotherapies both in a clinical trial (Project 1) and in preclinical mouse models (Project 2). We propose to
study novel immunosuppressive pathways in human GBMs based on CD161/ Clec2D (Project 3), IL-27 and
endogenous glucocorticoid signaling (Project 4) and understand how these can be overcome to improve the
anti-tumor function of CD4 and CD8 effector T cells. Core services will provide sophisticated genomic (Core 1),
biocomputational/ biostatistical (Core 2), and mouse modeling/ imaging (Core 3) approaches to these Projects.
This Program Project will thus provide significant mechanistic insights into the immunosuppressive
microenvironment of GBM, into preclinical avenues of how to activate T cells against these tumors and finally
into a novel clinical trial to target personalized GBM neoantigens in humans.

## Key facts

- **NIH application ID:** 10876404
- **Project number:** 5P01CA236749-05
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** E. Antonio Chiocca
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,680,832
- **Award type:** 5
- **Project period:** 2020-07-03 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876404

## Citation

> US National Institutes of Health, RePORTER application 10876404, Understanding and Overcoming T cell Immunosuppression in Glioblastoma (5P01CA236749-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10876404. Licensed CC0.

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