# Unraveling the influence of genetic subtype on spatial configurations of tissue and immune compartment composition in clear cell renal cell carcinoma

> **NIH NIH F31** · HARVARD UNIVERSITY · 2020 · $37,734

## Abstract

Abstract
Clear cell renal cell carcinoma (ccRCC) is a highly vascularized and immune infiltrated cancer,
and is responsible for the majority of deaths caused by kidney cancer. Notably, ccRCC is
defined by clear mutational events, starting with VHL loss, and followed by loss of an epigenetic
regulator (e.g. BAP1, PBRM1) on chromosome 3p. While clinical studies have associated BAP1
driven tumors with worse prognosis relative to PBRM1 driven cases, at present histological
grade is the only feature distinguishing these subtypes. Moreover, attempts to study the gene
expression characteristics of renal cell carcinoma have been limited to tumor cells, leaving the
precise role of the immune compartment in disease progression uncharacterized, especially in
relation to genetic driver subtype. Here, I present a set of complementary approaches to
examine the relationship between genetic subtype and phenotype in ccRCC at the tissue and
molecular levels. In Aim 1, I will develop a model to create condensed representations of
ccRCC slide images to identify underlying spatial configurations of tissue, and how they vary
across BAP1 and PBRM1 driven tumors. In Aim 2, I will focus on the immune compartment —
the infiltrating and bordering immune populations of the tumor, and will identify patterns of gene
expression associated with both intrinsic and acquired resistance to immunotherapy. This work
stands to provide clarity on the relationship between driving genetic events and fundamental
renal cell carcinoma biology, and consequently has the potential to immediately impact clinical
decision making.

## Key facts

- **NIH application ID:** 9988045
- **Project number:** 1F31CA250136-01
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Jackson Nyman
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,734
- **Award type:** 1
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988045

## Citation

> US National Institutes of Health, RePORTER application 9988045, Unraveling the influence of genetic subtype on spatial configurations of tissue and immune compartment composition in clear cell renal cell carcinoma (1F31CA250136-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9988045. Licensed CC0.

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