# CCSG Supplement: Identifying Mechanisms of Treatment Resistance and Response in Kaposi Sarcoma (Biospecimen/Cohort)

> **NIH NIH P30** · FRED HUTCHINSON CANCER CENTER · 2024 · $104,167

## Abstract

SUMMARY/ABSTRACT
Kaposi sarcoma (KS) is a virally-driven malignancy caused by Kaposi sarcoma-associated herpesvirus (KSHV)
that remains a leading cause of global cancer-related morbidity and mortality among people living with HIV
(PLWH). In our ongoing prospective KS cohort in Uganda (the “HIPPOS” study), treatment outcomes remain
poor despite optimized treatment with antiretroviral therapy and chemotherapy, with an overall 1-year survival
of only 64% among the first 200 study participants. Importantly, however, we observed differential outcomes
among participants, with ~10% achieving a complete remission (CR), ~48% a partial response (PR), and ~25%
progressive disease (PD). Understanding the biologic mechanisms underlying these response differences
could inform the design of more effective therapies for KS.
Findings from several of our studies based on the HIPPOS KS cohort suggest that ongoing KSHV replication is
an important driver of KS tumorigenesis, and that KSHV expression profiles in KS tumors are likely modified by
HIV co-infection and the host immune infiltrate. We hypothesize that control of KSHV replication and
suppression of viral oncogenic gene products in KS tumors is necessary for KS tumor regression.
We now propose to build on these observations by evaluating how signatures of KSHV, HIV, and host immune
cell composition in KS tumors over time are associated with tumor response among participants in the
HIPPOS cohort. To date, the HIPPOS cohort has enrolled over 280 participants (including both HIV-associated
and HIV-negative KS), and we have established an extensive biorepository of clinically annotated specimens,
including more than 1,500 plasma samples and 1,350 KS tumor biopsies. Importantly, these samples are
collected serially before, during, and following treatment and linked to participant response assessments.
We now propose to leverage this unique cohort to assess changes that occur in KSHV, HIV, and host immune
signatures over the course of KS treatment and to determine how these signatures are related to KS tumor
regression or progression. We will use existing data from the HIPPOS cohort as well as perform RNA-
sequencing and multispectral immunohistochemistry on a subset of KS samples to characterize viral gene
expression and host immune responses in the KS tumor microenvironment (TME). Our specific aims are:
Aim 1. To determine if suppression of plasma KSHV replication over the course of treatment is associated with
improved KS response or survival.
Aim 2. To identify signatures of KSHV and HIV gene expression and host immune cell infiltration in KS tumors
that are associated with response to treatment.
Aim 3. To determine if the number and/or localization of tumor infiltrating lymphocytes (TIL) in the KS TME
associated with KS treatment response.

## Key facts

- **NIH application ID:** 11069847
- **Project number:** 3P30CA015704-49S5
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Thomas James Lynch
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $104,167
- **Award type:** 3
- **Project period:** 1997-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11069847

## Citation

> US National Institutes of Health, RePORTER application 11069847, CCSG Supplement: Identifying Mechanisms of Treatment Resistance and Response in Kaposi Sarcoma (Biospecimen/Cohort) (3P30CA015704-49S5). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11069847. Licensed CC0.

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