# Project 1: Blood Immunomethylomic Markers of Outcome in Glioblastoma Patients

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $540,401

## Abstract

Project Summary/Abstract
Glioblastomas (GBM) are devastating central nervous system tumors that are associated with an
immunosuppressive network impacting the tumor microenvironment, bone marrow and peripheral blood
compartments. The development of novel markers of cancer immunity have not kept pace with breakthroughs
in our understanding of cancer-associated inflammation and its relationship with abnormal hematopoiesis and
the production of myeloid derived suppressor cells. This gap in our understanding is a recognized high priority
in the new era of cancer immunotherapy. The Cancer Moonshot blue ribbon panel recommended as a key
actionable goal “to develop approaches to overcome an obstructive, immune-suppressive tumor environment
in both children and adults”. Our project addresses this important goal by developing and testing a highly
innovative approach for measuring immunosuppression in GBM patients. Our powerful method for immune
profiling that is based on unique immune cell DNA methylation fingerprints is more reproducible, and less
intrusive and costly than current methods. Using this novel immunomethylomic approach for immune profiling
in Aim 1 we will serially assess immune status in a large group of patients with newly diagnosed GBM from
their initial diagnosis through their surgery, radiation and chemotherapy treatments. At each of 5 time points we
will assess each patient's levels of immunosuppressive myeloid derived suppressor and other cell types
through the peripheral blood immune profile. To identify clinical correlates of treatment response and tumor
recurrence at each point we will also assess each patient's MRI scans. In Aim 2 we will then assess the
prognostic value of methylation generated immune profiles (myeloid derived suppressor cells, CD4, CD8, T-
cells, B-cells, NK, monocytes, and neutrophils) and other factors in GBM patient survival and progression. In
Aim 3 we will evaluate how the new information on patient immune profiles can influence clinical decision
making. We will build comprehensive statistical models that include relevant clinical variables to predict patient
survival and tumor progression as well as combined models that include both immune factors and clinical
variables. Rigorous comparisons of purely clinical versus combined models (which include immune factors) will
be evaluated and will reveal how immune profiles can improve GBM outcome prediction. The end result of
these studies will enable clinicians and patients to better understand their prognosis and improve risk
stratification for future clinical trials. Improved predictions of tumor progression will help to avoid unnecessary
interventions that may be invasive and potentially harmful. Incorporation of DNA based assessment of immune
factors in prognostic models of GBM survival and progression will provide a major advance in patient
management and outcomes.

## Key facts

- **NIH application ID:** 9999429
- **Project number:** 5P50CA097257-18
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** John K. Wiencke
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $540,401
- **Award type:** 5
- **Project period:** 2002-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999429

## Citation

> US National Institutes of Health, RePORTER application 9999429, Project 1: Blood Immunomethylomic Markers of Outcome in Glioblastoma Patients (5P50CA097257-18). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9999429. Licensed CC0.

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