# Deciphering the role of tumor-macrophage crosstalk during metastatic dissemination to the peritoneum

> **NIH NIH K00** · WASHINGTON UNIVERSITY · 2024 · $103,352

## Abstract

Project Summary/Abstract:
In the past decade, checkpoint blockade immunotherapies have greatly improved the overall survival of
advanced melanoma patients. However, these therapies have failed to treat many other cancer types, including
cancers of the pancreas, liver, and stomach. Understanding the successful tumor protective immune responses
in long term cancer survivors could promote the understanding of anti-tumor immune responses and the
development of novel therapeutic strategies. Melanoma patients who developed dermal immune-related adverse
events (irAEs), including rash and vitiligo, have better overall survival than those unaffected patients. However,
the immune mechanisms linking dermal irAEs with exceptional anti-tumor immunity remain unknown. Thus,
specific aim 1 will comprehensively characterize the phenotype, persistence, antigen specificity, and localization
of anti-tumoral T cell responses in both vitiligo and rash affected melanoma survivors using single-cell RNA-seq,
single-cell TCR-seq, bulk TCR-seq and 10X spatial transcriptomics. I hypothesize that compared to unaffected
melanoma patients, dermal irAE patients maintain more durable proinflammatory T cell responses with a more
tumor-focused TCR repertoire. This project will be conducted at the Norris-Cotton Cancer Center (NCCC), well
supported by a collaborative team including medical oncologist, surgeon, dermatologist and immunologist. The
Sponsor’s lab houses expertise in tumor immunology, memory T cell and translational research and the sponsor
has rich experiences in mentoring graduate students. The trainings will be focused on knowledge and novel
technical skills such as the 10X spatial transcriptomics to successfully finish the research project. In addition,
developing professionals for the transition to the K00 phase is also an important training objective. Transitioning
to the K00 phase, the research focus will be cancer immunotherapy resistance mechanisms and the
development of novel immunotherapeutic strategies that leverage microbiome. Intratumoral microbiomes were
recently found to promote successful tumor immunity even in ‘immune-cold’ cancer types, yet the exact molecular
and cellular mechanisms remain unknown. I hypothesize that certain microbiomes could reprogram immune
cells and the tumor cells themselves, leading to a more proinflammatory anti-tumor microenvironment. The
research will be conducted in an outstanding cancer immunology lab combining leaderships in both translational
human research and mechanistic fundamental studies in pre-clinical models. The research trainings will be
focused on using mouse models, genomics, epigenomics, metabolomics and cellular immunology approaches
to identify the critical mechanisms to overcome immunotherapy resistant cancer growth. The goal by the end of
the F99/K00 trainings is to understand the features of tumor protective immune responses and the optimal design
of novel cancer immunotherapies. These trainings will provi...

## Key facts

- **NIH application ID:** 10850581
- **Project number:** 5K00CA264434-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jichang Han
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $103,352
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10850581

## Citation

> US National Institutes of Health, RePORTER application 10850581, Deciphering the role of tumor-macrophage crosstalk during metastatic dissemination to the peritoneum (5K00CA264434-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10850581. Licensed CC0.

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