# Role of Ly6K in TGF-beta and immune escape pathways of triple negative breast cancer

> **NIH NIH R01** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 2021 · $399,241

## Abstract

Project Summary/abstract
We have identified that increased expression of Ly6K is associated with poor outcome in triple negative breast
cancer (TNBC). Mechanistically, Ly6K is required for activation of TGFβ signaling and increased expression of
the immune checkpoint protein PD-L1. We propose that the biomarker Ly6K is an ideal therapeutic target for the
treatment of TNBC because this protein is not expressed in normal cells, except in testis, and it is not required
for vital organ function, except for spermatogenesis. Thus, targeting this protein for the treatment of TNBC, a
disease affecting mostly females, is appropriate and ideal. We have identified small drug-like molecules, which
specifically bind to Ly6K and inhibit in vivo tumor growth. Mechanistically, they inhibit TGFβ signaling and PD-
L1 expression in TNBC cells in an Ly6K dependent manner. In this proposal, we plan to validate these potential
novel therapeutics in a humanized PDX model. This proposal will reveal the missing signaling links downstream
of Ly6K, which activate TGFβ signaling and increase PD-L1 expression. We anticipate that the findings from our
research will transform the field of developmental therapeutics concerning treatment of TNBC by defining Ly6K as
a novel therapeutic target for anti-TGFβ signaling and inhibition of PD-L1 expression.

## Key facts

- **NIH application ID:** 10229403
- **Project number:** 5R01CA227694-04
- **Recipient organization:** HENRY M. JACKSON FDN FOR THE ADV MIL/MED
- **Principal Investigator:** Geeta Upadhyay
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $399,241
- **Award type:** 5
- **Project period:** 2018-08-03 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229403

## Citation

> US National Institutes of Health, RePORTER application 10229403, Role of Ly6K in TGF-beta and immune escape pathways of triple negative breast cancer (5R01CA227694-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10229403. Licensed CC0.

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