# Mechanistic Dissection and Therapeutic Targeting of B7x in Cancer

> **NIH NIH F30** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2022 · $51,752

## Abstract

PROJECT SUMMARY/ABSTRACT
Immune checkpoints are proteins that regulate the body’s immune system via inhibition of immune cells. In
diseases such as cancer, these same pathways may be commandeered in order to inappropriately inhibit
immune responses. One approach to overcome this excessive inhibition and restore normal immune function
is to physically block these inhibitory proteins using monoclonal antibodies (mAbs), a strategy known as
immune checkpoint blockade. Our lab discovered the protein B7x (VTCN1/B7S1/B7-H4), an immune
checkpoint whose regulation and mechanism of action are still being elucidated. B7x is expressed on a wide
variety of cancers and is associated with poor clinical outcomes. It has been shown to inhibit effector T cell
functions such as cytokine production and proliferation, and promotes T cell exhaustion; it has also been
associated with tumor infiltration of immunosuppressive cell populations such as myeloid derived suppressor
cells (MDSCs). Intriguingly, it is not typically co-expressed with the well-studied immune checkpoint PD-L1,
and blocking B7x using anti-B7x mAbs improves anti-tumor responses and survival in mouse models. This
suggests that B7x holds a non-overlapping but key role in cancer immune evasion. For these reasons I
hypothesize that B7x mediates immune evasion through inhibiting effector cell functions while
simultaneously promoting immunosuppressive cells and is therefore a promising target for cancer
immunotherapy. Thus, we propose the following two aims: 1) Examine the mechanisms that regulate B7x
expression and its role on MDSCs; and 2) Develop and characterize a new anti-B7x immunotherapy. In aim 1 I
will examine the how hypoxia and other tumor microenvironment-associated cytokines regulate B7x
expression. In addition, I will explore how B7x affects the immunosuppressive MDSC cell population
generation and survival. In aim 2 I will test the anti-tumor efficacy of newly generated anti-B7x mAb-based
immune checkpoint blockade in vivo using metastasis and spontaneous models of lung cancer. We will also
characterize how this new immunotherapy alters T cell phenotypes using flow cytometry and single-cell RNA
sequencing. Finally, we will explore if combining our anti-B7x mAb with anti-TIM3 and anti-PD1 mAbs confers
superior anti-tumor efficacy than anti-B7x monotherapy in vivo. Together, these studies will allow us to broadly
explore the role of B7x in tumorigenesis and therapeutic potential of anti-B7x immunotherapy, and combined
with a personalized training plan and supportive research environment at Einstein, cultivate the skills required
of a physician-scientist.

## Key facts

- **NIH application ID:** 10464896
- **Project number:** 5F30CA265130-02
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Christopher D Nishimura
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2021-08-16 → 2024-08-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464896

## Citation

> US National Institutes of Health, RePORTER application 10464896, Mechanistic Dissection and Therapeutic Targeting of B7x in Cancer (5F30CA265130-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10464896. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*