1982P - Transcriptomic analysis and tumor microenvironment (TME) classification reveals unique immune biology in HIV patients with Kaposi sarcoma (KS)

Background

KS, associated with human herpesvirus 8 (KSHV) infection, is a tumor originating from endothelial cells. As a common tumor associated with AIDS, KS is typically more aggressive in HIV-positive (HIV+) than in HIV-negative (HIV-) patients (pts). While antiretroviral therapy helps control KS in HIV+ pts, chemotherapy remains the first-line treatment (Tx) in advanced KS but is limited by modest responses and dose-limiting toxicities. The TME has been shown to play a critical role in KS development and progression. Here, we sought to understand the TME in KS, with a specific focus on the differences in HIV status.

Methods

Whole transcriptomic profiling was performed on 13 retrospective samples from 9 pts (HIV+: n = 6, HIV- n =3; mostly baseline, except 2 HIV- and 2 HIV+ pts had paired samples before and after Tx). A deconvolution algorithm Kassandra was used to predict cellular composition with pre-training on sarcoma samples, and EdgeR was used for differential expression analysis. TME subtypes were classified based on a previous study (Bagaev et al., 2021) assessing sarcoma-related gene expression patterns.

Results

All KS samples were enriched with endothelial cells and had characteristics of a typical sarcoma TME with an abundance of macrophages and normal amounts of B cells. Most HIV- pts had an Immune-Enriched, Non-fibrotic subtype, while HIV+ pts had immune-Enriched, Fibrotic or Fibrotic TMEs. Decreased angiogenic signatures were observed after Tx in HIV+ pts with paired samples. Expression levels of chemokines (CXCL2, CXCL8, CXCL11), chemokine receptors (CCR1-7, CXCR1-2), and CCL factors were higher in pre-Tx HIV- pts versus post-Tx and post-TX HIV+ pts versus pre-TX. PD-L1 and PD-L2 expressions were higher in HIV- pts before Tx and in HIV+ pts after Tx. In 3 HIV- and 2 HIV+ pts, for whom TCR.

Conclusions

Our results showed distinct transcriptomic features and TMEs between HIV+ and HIV- KS in responses to Tx. Future larger cohorts and research into the unique T cell clonotypes may help yield novel therapeutic avenues in KS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

BostonGene, Corp. and Albert Einstein College of Medicine.

Funding

BostonGene, Corp.

Disclosure

A. Sevkoplyas, S. Podsvirova, A. Tyshevich, K. Zornikova, N. Shin, N. Kotlov, E. Postovalova: Financial Interests, Institutional, Full or part-time Employment: BostonGene, Corp.; Financial Interests, Institutional, Stocks/Shares: BostonGene, Corp.. L. Paoluzzi: Financial Interests, Institutional, Full or part-time Employment: Regeneron; Financial Interests, Institutional, Stocks/Shares: Regeneron. All other authors have declared no conflicts of interest.