# Aging, immunosenescence and glioblastoma

> **NIH NIH K02** · NORTHWESTERN UNIVERSITY · 2020 · $144,936

## Abstract

PROJECT SUMMARY
Advanced aging is the primary factor associated with an adult diagnosis of glioblastoma (GBM) with wild-type
isocitrate dehydrogenase; constituting 90% of all GBM diagnoses and the most commonly aggressive primary
brain tumor of the central nervous system (CNS). Adult GBM is associated with a median overall survival (OS)
of 15 months and the prognosis significantly decreases with progressive aging. Since standard of care treatment
including maximal surgical resection, radiotherapy, and chemotherapy with temozolomide (TMZ) inevitably leads
to a 100% mortality rate, immunotherapy has been proposed as a potential future approach for GBM patients,
based on its success in treating patients with other aggressive cancers. However, in contrast to the growing list
of end-stage malignancies that respond beneficially to anti-PD-1 mAb and/or anti-CTLA-4 mAb treatment,
patients diagnosed with GBM and treated with immunotherapy have thus far failed to demonstrate an improved
survival among all phase III clinical trials to-date. The goal of my K02 application is therefore to define the
advanced aging-dependent increase of immunosuppressive factors that inhibit the anti-GBM immune response,
as well as to understand how aging-increased immunosuppressive indoleamine 2,3 dioxygenase 1 (IDO1) non-
canonically decreases the response to immunotherapy. Previous work from my group discovered that, advanced
aging increases immunosuppressive IDO1 gene expression in the normal human and mouse brain. We also
showed that, immunotherapeutic treatment combining radiotherapy (RT) with anti-PD-1 mAb and an IDO1
enzyme inhibitor, leads to a long-term (≥150 days) survival benefit in 6-12 week old immunocompetent mice with
intracranial GBM. Strikingly, the treatment was made significantly less effective at improving survival in older
subjects when engrafted the exact same tumor cells. My working hypothesis is that, advanced aging increases
immunosuppression in the CNS that limits immunosurveillance mechanisms responsible for preventing
GBM cell outgrowth and suppressing immune system responsiveness to immunotherapy. The protected
time during K02 support will allow for comprehensive aging-specific training, high-level interactions with an expert
committee of scientists that have broad experience exploring the interactions between aging, cancer, and/or the
immune response, and will provide me with the necessary time to develop competitive R01 applications to
support a future program of research focused on aging in the setting of GBM; a disease that remains incurable.

## Key facts

- **NIH application ID:** 10039857
- **Project number:** 1K02AG068617-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Derek Alan Wainwright
- **Activity code:** K02 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $144,936
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10039857

## Citation

> US National Institutes of Health, RePORTER application 10039857, Aging, immunosenescence and glioblastoma (1K02AG068617-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10039857. Licensed CC0.

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