Angiogenesis, programmed death ligand 1 (PD-L1) and immune microenvironment association in laryngeal carcinoma

In the specific field of laryngeal carcinoma (LSCC), evidence about the interaction between angiogenetic pathway and immune microenvironment has not yet been explored. Given the potential relevance of such an interaction for prognostic and therapeutic purposes, the main aim of this exploratory study was to investigate the existence of a correlation between angiogenesis (quantified through CD31 expression), programmed cell death ligand 1 (PD-L1) expression, and immune microenvironment. A secondary aim was to verify whether considering a combination of angiogenesis and immune microenvironment variables might improve prognostic accuracy compared to the traditional clinical-pathological prognostic tools. CD31-assessed micro-vessel density (MVD), PD-L1 in terms of combined positive score (CPS), and tumour infiltrating lymphocytes (TILs) were assessed on 45 consecutive cases of LSCC. Cox proportional hazards model revealed increasing CD31-assessed MVD values, PD-L1 CPS <1, and TILs count rate <30%, as predictive of reduced disease free survival (DFS). Multivariate analysis found that MVD (p<0.0001) and TILs (p=0.0420) retained their significant independent prognostic value. Spearman's correlation model disclosed a significant negative correlation between CD31-assessed MVD values and PD-L1 CPS (p=0.0040). PD-L1 CPS and TILs count rate were positively correlated (p 0.0001). DFS was significantly lower in the CD31assessed MVD 7, PD-L1 CPS 1, TILs >30% group (p=0.0001). These data preliminarily support an integrated interpretation of the prognostic role or angiogenesis and immune microenvironment markers in LSCC. This is of potential clinical relevance suggesting a synergistic effect of the combination of anti-angiogenic drugs with programmed death-1/PD-L1 checkpoint inhibitors in advanced LSCC.

Automated summary

The study aimed to investigate the correlation between angiogenesis, PD-L1 expression, and immune microenvironment in LSCC and found that CD31-assessed MVD and TILs had independent prognostic value. There was a significant negative correlation between CD31-assessed MVD values and PD-L1 CPS, while PD-L1 CPS and TILs count rate were positively correlated. The integrated interpretation of these markers may have clinical relevance for a synergistic effect of combining anti-angiogenic drugs with PD-1/PD-L1 checkpoint inhibitors in advanced LSCC.