In depth characterisation of the tumour microenvironment reveals HHV-8 dependent immune regulation in HIV-associated and classic Kaposi Sarcoma.

BackgroundKaposis sarcoma (KS) is the most common malignancy occurring in people living with HIV (PLWH). The clinical course of KS in PLWH established on combined anti-retroviral therapy (cART) resembles that of classic KS. However, no studies have so far been conducted to compare clinical and immunologic characteristics of these subtypes. ObjectivesTo compare the clinical and biological characteristics of HIV-associated KS in patients with well-controlled viral infection (N=21) and non-HIV associated KS (N=19). MethodsClinical data were prospectively collected from patients treated at the National Centre for HIV malignancies at Chelsea & Westminster Hospital. Archival tumour samples were retrieved to perform targeted transcriptomic analysis using the Nanostring nCounter platform. The results were validated by multiplex immune-fluorescence. ResultsMedian progression free survival (mPFS) was comparable between groups. The tumour microenvironment (TME) of non-HIV associated KS was characterized by upregulation of pathways associated with adaptive and innate immunity and angiogenesis. Transcripts relating to glycolysis and endothelial to mesenchymal transition were upregulated in the TME of HIV-associated cases. Furthermore, the TME of HIV-associated cases was associated with lower infiltration of CD4 activated cell. In both cohorts, we found the expression of HHV-8 genes to positively correlate with activated CD4, CD8, NK and immune checkpoints gene expression. ConclusionsIn conclusion, we showed that the TME of KS in the presence of well-controlled HIV infection is characterized by a lower degree of inflammation and more pronounced epithelial to mesenchymal transition. We also identified intra-tumoral HHV-8 gene expression as a driver of TME composition.