# The B7x pathways in the tumor microenvironment

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2021 · $398,901

## Abstract

The B7x pathway in the tumor microenvironment
 During the first five years of the R01 funding period (April 2014 – March
2019), we produced 37 publications and received 3 granted patents. We made
major discoveries on function and structure of B7x, a much less studied B7 family
member that was originally discovered by us.
 Immune checkpoint blockade of PD-1/PD-L1 and CTLA-4 have advanced
the treatment of cancer patients. However, one of the biggest challenges is that
the majority of cancer patients do not respond to these treatments. Clearly, new
strategies targeting additional immune checkpoints are needed to improve the
immunotherapy of human cancers.
 Our basic and clinical studies and crystal structure analysis suggest B7x
immune checkpoint has very different mechanisms and provides an excellent
target to develop new immunotherapies. Furthermore, we recently discovered
HHLA2 as a homolog of B7x and a new member of the B7 family, which provides
a unique opportunity to study a new human immune checkpoint. Thus, our
central hypothesis is that B7x and HHLA2, two less-studied members of the B7
family originally discovered by us, are critical immune evasion pathways within
the tumor microenvironment and are therapeutic targets for new cancer
immunotherapies. This hypothesis will be tested by pursuing three aims: 1)
Dissect molecular and cellular mechanisms by which tumor-expressed B7x
induces immunosuppression within the tumor microenvironment; 2) Develop new
immune checkpoint blockade targeting B7x: Combination therapies and
mechanisms; and 3) Elucidate the HHLA2 pathway: A new homology of B7x. We
have generated a number of novel tools which provides us with unique
opportunities to address challenges and realize goals. The outcomes of this
project will reveal new immune evasion mechanisms in the tumor
microenvironment and will establish the foundation for clinical design of new
immunotherapies, which could potentially be effective in tumors that resist
current PD-1/PD-L1 and CTLA-4 targeted therapies.

## Key facts

- **NIH application ID:** 10116632
- **Project number:** 2R01CA175495-08A1
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Xingxing Zang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $398,901
- **Award type:** 2
- **Project period:** 2014-07-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116632

## Citation

> US National Institutes of Health, RePORTER application 10116632, The B7x pathways in the tumor microenvironment (2R01CA175495-08A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10116632. Licensed CC0.

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