# Cisplatin Mediated Immune Modulation of HPV Positive Head and Neck Cancer

> **NIH NIH P20** · SANFORD RESEARCH/USD · 2020 · $283,507

## Abstract

PROJECT SUMMARY
While head and neck squamous cell cancer (HNSCC) is only 5% of all cancers in the United States, the
incidence of a subset of HNSCC caused by human papilloma virus (HPV) is increasing rapidly. Conventional
treatment of these cancers requires chemotherapy (usually Cisplatin) and radiation. While the HPV positive
HNSCC have an improved response to treatment, the overall 5 year survival for HNSCC is only 50% and the
short and long term side effects from treatment are significant. Modulation of current effective treatment and
new less toxic treatments are needed to improve the long term cures as well as limit the side effects in a
progressively younger cancer population that may live with these side effects for 30 to 40 years post treatment.
We have previously shown a directed adaptive immune response to HPV positive HNSCC in a mouse model
and the importance of the immune response to HPV positive HNSCC has been confirmed in correlative human
studies as well. While cisplatin has been described as interfering with DNA, we have found some preliminary
evidence for a potential immune stimulating mechanism through a cellular protein, CD154. We have found
that the CD154-CD40 interaction, classically described in B and T cell interactions, is required for the
clearance of tumors in our model. CD154 is present in human and mouse HNSCC lines and increases after
cisplatin treatment. Our hypothesis is cisplatin causes an increase of CD154 in the tumor cell that
results in immune mediated clearance of HPV positive HNSCC. This project proposes to define the
interaction of the tumors cells and the immune system, determine the mechanism that cisplatin uses to
increase CD154, and to improve this cisplatin driven immune clearance through off the shelf immune
modulating agents. This project is designed to 1) provide more information about the specific components of
the immune system in and around the tumor that are affected by this increase in CD154 through Cisplatin
treatment 2) understand the mechanism that Cisplatin uses to increase CD154 in HPV positive tumor cells
and 3) Combine immune modulation with Cisplatin treatment in our mouse model of HPV positive HNSCC.
This immune modulation will utilize off the shelf antibody and vaccine treatments that are already in clinical
application or within a few years of clinical implementation in humans. The data from this project will provide a
greater understanding of a common chemotherapy agent, Cisplatin, that may prompt use of the drug in doses
and timing that could improve the efficacy of treatment and potentially the long term response of HPV positive
cancers. The knowledge gained from this study could be potentially applied to other HPV positive cancers
(cervical, anal, etc.) as well as perhaps HPV negative cancers responsive to cisplatin. The long term goal of
this project is to understand the modulation of the local tumor environment and to use this information to find
treatment regimens that cure pat...

## Key facts

- **NIH application ID:** 9985854
- **Project number:** 5P20GM103548-10
- **Recipient organization:** SANFORD RESEARCH/USD
- **Principal Investigator:** William Charles Spanos
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $283,507
- **Award type:** 5
- **Project period:** 2011-09-02 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985854

## Citation

> US National Institutes of Health, RePORTER application 9985854, Cisplatin Mediated Immune Modulation of HPV Positive Head and Neck Cancer (5P20GM103548-10). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/9985854. Licensed CC0.

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