Clinical implications of systemic and local immune responses in human angiosarcoma

摘要

Angiosarcomas are a rare subtype of soft-tissue sarcomas which exhibit aggressive clinical phenotypes with limited treatment options and poor outcomes. In this study, we investigated the clinical relevance of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic immune response, as well as its correlation with intra-tumoral immune profiles in a subgroup of cases (n?=?35) using the NanoString PanCancer IO360 panel and multiplex immunohistochemistry. In the overall cohort (n?=?150), angiosarcomas of the head and neck (AS-HN) comprised most cases (58.7%) and median overall survival (OS) was 1.1 year. NLR, classified as high in 78 of 112 (70%) evaluable patients, was independently correlated with worse OS (HR 1.84, 95%CI 1.18–2.87, p?=?0.0073). Peripheral blood NLR was positively correlated with intra-tumoral NLR (tNLR) (Spearman’s rho 0.450, p?=?0.0067). Visualization of tumor-infiltrating immune cells confirmed that tNLR scores correlated directly with both neutrophil (CD15+ cells, rho 0.398, p?=?0.0198) and macrophage (CD68+ cells, rho 0.515, p?=?0.0018) cell counts. Interestingly, tNLR correlated positively with oncogenic pathway scores including angiogenesis, matrix remodeling and metastasis, and cytokine and chemokine signaling, as well as myeloid compartment scores (all p??0.001). In patients with documented response assessment to first-line chemotherapy, these pathway scores were all significantly higher in non-responders (47%) compared to responders. In conclusion, systemic and local immune responses may inform chemotherapy response and clinical outcomes in angiosarcomas.