427P - On the clinical implications of systemic and local immune responses in human angiosarcoma

Background

Angiosarcomas are a rare subtype of soft-tissue sarcomas which exhibit aggressive clinical phenotypes with limited treatment options and poor outcomes.

Methods

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 using the NanoString PanCancer IO360 panel and multiplex immunohistochemistry.

Results

In the overall cohort (n=150), angiosarcomas of the head and neck 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), along with age >65 years and distant metastasis at diagnosis. 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 remodelling & metastasis and cytokine & chemokine signaling, as well as myeloid compartment scores (all p<0.001). In patients with documented best clinical responses to first-line chemotherapy (n=60), these pathway scores were all significantly higher in non-responders (47%) compared to responders.

Conclusions

These findings suggest that systemic and local immune responses may inform clinical outcomes in angiosarcomas.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

SingHealth Duke-NUS Oncology ACP.

Disclosure

All authors have declared no conflicts of interest.