# Interplay of natural killer cells and extracellular matrix proteins in solid cancers

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $660,987

## Abstract

Project Summary/Abstract:
Natural killer (NK) cells have long been known to provide critical early defense against viral infections and
malignancies. Nevertheless, most of the clinical success associated with using NK cells has been restricted to
hematological malignancies, which can be partly attributed to the defective NK cell activation in peripheral
tissues. Extracellular matrix (ECM) proteins are present in all peripheral tissues where they maintain
homeostasis by providing scaffold as well as important developmental cues to the surrounding cells. We have
recently discovered a critical role for ECM proteins in switching the function of conventional NK cells as they exit
the circulation and enter the peripheral tissues. We aim to investigate how ECM proteins regulate NK cell
functions in the skin and solid cancers. Skin and breast cancer are the leading cause of cancer morbidity and
mortality in the United States. These cancers frequently develop primary and secondary resistance to current
immunotherapeutics. In addition, chemotherapies for them cause wide-ranging side effects and thus significantly
burden the health care system. Defective ECM turnover is a hallmark of skin, breast, and other solid cancers.
To fully elucidate the bi-directional interactions between NK cells and ECM in the context of solid cancer
development, we aim to (1) Determine the mechanism of collagen-induced loss of NK cell killing function in solid
cancers, (2) Determine the role of collagen-III in the regulation of NK cell helper function in solid cancers, and
(3) Examine the impact of other major ECM proteins on NK cell functionality. The outcomes of the proposed
studies will reveal novel mechanisms of ECM-NK cell interactions in cancer. Our research will greatly facilitate
the development of novel therapeutic strategies to harness NK cells for the treatment of solid cancers.

## Key facts

- **NIH application ID:** 10879349
- **Project number:** 1R01CA276115-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Shadmehr Demehri
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $660,987
- **Award type:** 1
- **Project period:** 2024-04-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10879349

## Citation

> US National Institutes of Health, RePORTER application 10879349, Interplay of natural killer cells and extracellular matrix proteins in solid cancers (1R01CA276115-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10879349. Licensed CC0.

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