# KSHV,HIV and the Kaposi's Sarcoma Tumor Niche

> **NIH NIH R01** · LSU HEALTH SCIENCES CENTER · 2021 · $10,399

## Abstract

PROJECT SUMMARY
Epidemic Kaposi’s sarcoma (KS) is an HIV-1 associated tumor, and remains one of the highest incidence
neoplasms in sub-Saharan African men and women despite effective antiretroviral therapy (ART) programs.
The fundamental mechanism driving KS appears to be KSHV infection, but it is clear that KSHV infection alone
is insufficient for KS development since most infected individuals do not develop KS. HIV-1 co-infection or
therapeutic immune suppression induces, exacerbates, or accelerates KS disease. How HIV-1 co-infection
synergizes with KSHV to form or maintain the tumor niche is largely unexplored in tissue.
In many cancers, a clear understanding of the tumor microenvironment including the presence, antigen-
specificity and functionality of tumor-infiltrating lymphocytes (TILs) is revolutionizing therapeutic approaches.
Yet for KS we have a dearth of information about the nature of TILs and whether the tumor microenvironment
is suppressing their anti-neoplastic function in an HIV-1 dependent manner. This project seeks to rectify this
knowledge gap in a Case (HIV-1+/KS+) versus Control ((HIV-1+/KS-) design by comparatively investigating
the phenotypes and the functionality of TILs in comparison to the same cells in the peripheral immune system
and by comparing the tumor and peripheral immune cell expression patterns.
Our hypothesis is that even in the face of a detectable KSHV-reactive peripheral T cell response and effective
HIV-1 suppression, there are insufficient numbers of KSHV Ag-specifc tumor-infiltrating T lymphocytes (TILs)
and these cells are non-responsive to antigen in KS tumors. Our approach is 1) to functionally compare the
peripheral CD4 and CD8 T cell responses to KSHV and ubiquitous immunodominant antigens in KS with
differential HIV-1 disease duration; 2) to isolate, and immunophenotypically and functionally characterize KS
tumor infiltrating leukocytes; and 3) to compare the transcriptomes of TILs with autologous peripheral cells or
those from KS asymptomatic controls.
From these comparative investigations, we anticipate deriving a more robust understanding of the expression
programs and immune responsiveness of adaptive immune cells in the KS tumor niche and more complete
understanding of the role of HIV-1, immune suppression, anergy, exhaustion, and senescence in defining that
niche. This understanding will direct interventional strategies including the design of immunotherapeutics and
potentially vaccines against KS.

## Key facts

- **NIH application ID:** 10530977
- **Project number:** 7R01CA228178-05
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** John T. West
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $10,399
- **Award type:** 7
- **Project period:** 2018-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10530977

## Citation

> US National Institutes of Health, RePORTER application 10530977, KSHV,HIV and the Kaposi's Sarcoma Tumor Niche (7R01CA228178-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10530977. Licensed CC0.

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