# Discerning mechanisms of semaphorin 7A-mediated tumor progression via immunoevasion

> **NIH NIH K00** · UNIVERSITY OF COLORADO DENVER · 2024 · $99,022

## Abstract

Project
We
Summary/Abstract
have identified that semaphorin 7a (SEMA7A)—a signaling molecule that activates integrin-β1 signaling in
cancer—is upregulated in postpartum breast cancer (PPBC) and is associated with increased lymphatic
vessel
density (LVD), tumor-associated macrophages (TAMs), and metastasis. Additionally, SEMA7A+ tumors
recapitulate the accelerated tumor progression observed in PPBC and high SEMA7A expression correlates with
decreased survival. As such, PPBCs likely only represent a subset of SEMA7A+ cancers; there are currently no
therapies targeting SEMA7A.
cell
are
SEMA7A+BC,
SEMA7A+ breast cancers exemplify four key hallmarks of cancer: 1) resistance to
death, 2) angiogenesis and lymphangiogenesis, 3) immune evasion, and 4) invasion and metastasis; TAMs
implicated n each and in creating a pro-tumor microenvironment (TME). As TAMs and LVD are amplified in
 it is probable that they contribute to the worse prognosis of PPBC.
the F99 portion of this grant, my goals
i
In are to: 1) investigate SEMA7A-mediated alterations immune
cells of the TME in relation to mechanisms of antitumor immunity, 2) dissect SEMA7A-induced mechanisms that
govern tumor cell migration, and 3) determine if monoclonal antibody-induced inhibition of SEMA7A impedes
tumor growth and immune suppression. I will define the mechanisms of SEMA7A-induced effects on immune
cells of the TME that promote immunoevasion. I will also establish whether monoclonal antibody-induced
inhibition of SEMA7A impedes tumor growth and immune suppression. The results of these studies will identify
how SEMA7A promotes tumor progression, immunosuppression, and lymphatic-meditated metastasis, as well
as offer insight for future therapies to target SEMA7A+ breast cancers and provide insight to mechanisms of
immunoevasion in similar cancers, such as (PDAC) and advanced stage renal cell carcinomas (RCC).
RCC,
to
endure
immunotherapy
expertise
immune
progress
the K00 portion of this grant, will expand my interest in mechanisms of immunoevasion to PDAC and
which are highly aggressive cancers with elevated tumor heterogeneity, therapy resistance, and resistance
 antitumor immune responses. The mechanisms by which PDAC and RCC evade the immune system and
immunotherapy remain to be discovered. I propose to identify novel mechanisms of immunoevasion and
resistance in PDAC and RCC, with an initial focus on SEMA7A. I will seek K00 laboratories with
 in tumor immunology, immunotherapy, ex vivo models, and knowledge of dysregulated signaling within
cells. These studies will provide crucial insight into how highly aggressive tumors like PDAC and RCC
resulting in dismal prognoses and identify potential cells and mechanisms for future immunotherapies.
In I

## Key facts

- **NIH application ID:** 11142783
- **Project number:** 4K00CA284276-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Alan Michael Elder
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $99,022
- **Award type:** 4N
- **Project period:** 2024-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11142783

## Citation

> US National Institutes of Health, RePORTER application 11142783, Discerning mechanisms of semaphorin 7A-mediated tumor progression via immunoevasion (4K00CA284276-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11142783. Licensed CC0.

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