Abstract
This study aimed to evaluate plasma concentration of selected cancer-associated inflammatory and immune-modulated cytokines in HIV+ patients with advanced Kaposi sarcoma (KS), and to explore candidate biomarkers capable of predicting clinical outcome in response to chemotherapy (CT) plus combination antiretroviral therapy (cART).Thirty-seven plasma cytokines/chemokines were assessed by Luminex technology in 27 consecutive HIV+ KS patients, followed-up during CT and cART of maintenance (m-cART). Associations between plasma concentration of biomarkers and patient clinical response to m-cART were evaluated by means of Hazard Ratios (HRs) and corresponding 95% Confidence Intervals (CIs).Plasma baseline concentration of Granulocyte colony-stimulating factor (G-CSF), Hepatocyte growth factor (HGF) and endoglin were found to be associated with m-cART clinical response (HR:1.56, 95%CI:1.09-2.22, p = 0.01; HR:0.32, 95% CI:0.10-0.99, p = 0.05; HR:0.72, 95% CI:0.54-0.96, p = 0.03, respectively). The multivariate analysis confirmed the associations of baseline plasma G-CSF and HGF concentration with m-cART clinical complete remission response (HR:1.78, 95% CI:1.15-2.74, p = 0.009; HR:0.19, 95% CI:0.04-0.95, p = 0.04). Our exploratory study suggested that plasma G-CSF, HGF and endoglin may be novel predictors of clinical response during m-cART in HIV+ KS patients. Nonetheless, these findings should be further validated in an independent population study.
Highlights
Kaposi sarcoma (KS) is the most frequent malignant lesion in patients with AIDS, even after the widespread use of combination antiretroviral therapy, and it is characterized by spindle cell proliferation, inflammatory cell infiltration, angiogenesis, edema, and invasiveness [1, 2]
A statistically significant association with unfavourable clinical response to m-combination antiretroviral therapy (cART) was found for Granulocyte colony-stimulating factor (G-CSF) plasma concentration (HR:1.56, 95% Confidence Intervals (CIs):1.09–2.22; p = 0.01)
Plasma concentrations of Hepatocyte growth factor (HGF) (HR:0.32, 95% CI:0.10–0.99; p = 0.05) and of endoglin (HR:0.72, 95% CI:0.54–0.96; p = 0.03) were associated to favourable clinical response to maintenance anti-KS treatment (m-cART)
Summary
Kaposi sarcoma (KS) is the most frequent malignant lesion in patients with AIDS, even after the widespread use of combination antiretroviral therapy (cART), and it is characterized by spindle cell proliferation, inflammatory cell infiltration, angiogenesis, edema, and invasiveness [1, 2]. The complex aspect of this disease is probably supported by multiple concomitant pathogenetic factors. The most favoured model is that inflammatory cytokines and chemokines, possibly up-regulated by the Tat protein of HIV or the Kaposi sarcoma related herpesvirus (KSHV) infection, induce the expression of growth factors and act synergistically in promoting and sustaining cell proliferation [3, 4]. These involved biological factors can be released and they are detectable in the blood, mirroring the tumour microenvironment. Luminex multiparametric techonology has already been employed, in the setting of www.impactjournals.com/oncotarget
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