Cytokine profiles predict response and survival in treatment-naïve individuals with HIV-associated Kaposi sarcoma

Cytokine dysregulation is crucial to Kaposi sarcoma (KS) pathogenesis; however, its potential as a biomarker remains unclear. We evaluated associations between baseline cytokines and clinical outcomes in HIV-KS, a major cause of cancer morbidity and mortality in sub-Saharan Africa. Milliplex ® multiplex was used to measure baseline serum concentrations of 28 cytokines in 73 participants who were naïve to both ART and chemotherapy, with mainly advanced HIV-KS, randomised to receive antiretroviral therapy with or without chemotherapy (NCT00380770). The Wilcoxon rank-sum test assessed associations between cytokine levels and HIV-KS clinical features. The Kruskal-Wallis test evaluated cytokine concentrations in relation to treatment response at 3 and 12 months. Cox regression analysis evaluated the prognostic contribution of cytokines, with p ≤ 0.05 considered statistically significant. Lower MIP-1β concentrations were associated with poorer baseline immune status (CD4 counts < 150), p = 0.04. Higher eotaxin concentrations were associated with poorer clinical response, with highest levels observed in progressive disease (112.6 [62.6–146.6] pg/mL), followed by stable disease (83.8 [69.5–135.3] pg/mL), and lowest levels in those with an overall response (68.8 [52.5–80.7] pg/mL) ( p = 0.04). Increased levels of proinflammatory IL-6 and IL-8 were associated with reduced overall survival, with HRs of 1.49 (95% CI, 1.10–2.03, p = 0.01) and 1.83 (95% CI, 1.01–3.31, p = 0.045), respectively. Findings suggest that cytokine profiles contribute to the development and progression of HIV-KS, with high proinflammatory cytokines associated with poor treatment response and survival. Targeting these cytokines and pathways could lead to the development of novel, personalised, KS-specific treatment strategies to improve outcomes.