# Defining the role of CD26 in checkpoint blockaded induced tumor immunity

> **NIH NIH R21** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2021 · $103,533

## Abstract

Abstract:
The objective of this MPI R21 is to support an important discovery found by this basic T cell immunologist and
immune-therapist (Dr. Chrystal Paulos) and surgeon and scientist (Dr. David Neskey) research team in a
Phase II clinical trial (NCT03021993) in patients with oral cavity squamous cell carcinoma (OCC). These
patients were treated with Nivolumab as a novel neoadjuvant pre-surgical therapy at our institution (Hollings
Cancer Center). Our unpublished work reveals that a remarkable 44% of patients responded to this therapy via
pathological score. While promising, 56% of the patients remain unresponsive to this treatment. Our new data
reveals that responders express higher CD26 (co-stimulatory molecule with enzyme activity) on tumor-
infiltrating lymphocytes (TILs), while CD26 was far lower on TILs from non-responders. These data suggest
that CD26 plays a critical role in the function and migration of antitumor T cells to the oppressive tumor
microenvironment in patients responsive to PD-1 therapy. We propose to gain insight into CD26-expressing T
cells in the tumor, positing that the enzymatic CD26 activity augments the function, migration and antitumor
activity of human TILs (Aim 1) and that targeting this pathway can improve cancer immunotherapy in non-
responders: an idea we will explore in Aim 2, using our highly clinically relevant OCC tumor models. Overall,
the proposed research is expected to demonstrate that manipulation of the CD26 pathway may sufficiently
induce durable immunity against advanced OCC tumors and rescue patients non-responsive to PD-1 therapy.

## Key facts

- **NIH application ID:** 10162580
- **Project number:** 5R21DE029592-02
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** David M. Neskey
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $103,533
- **Award type:** 5
- **Project period:** 2021-05-01 → 2022-05-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10162580

## Citation

> US National Institutes of Health, RePORTER application 10162580, Defining the role of CD26 in checkpoint blockaded induced tumor immunity (5R21DE029592-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10162580. Licensed CC0.

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