According to the US National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results Program (SEER), the incidence of adenocarcinoma of the esophagus (EAC) is greatest in Caucasians, but is also prevalent in other ethnicities and mainly affects people over the age of 40. It occurs five times more frequently in men than women. The five-year survival rate is around 20% in the USA.
Immune checkpoint protein PD-L1 expression has been used to predict the clinical course of EAC in phase I clinical trials, however more markers are needed for improved clinical decision making. Matthew P. Humphries, Stephanie G. Craig, Jacqueline James and Manuel Salto-Tellez of Queen’s University, Belfast, UK, and colleagues, investigated the immunohistochemical expression of various T-cell lineage markers and other immune checkpoint biomarkers. Their influence in combination on EAC outcome was reported in the journal BMC Cancer.
Tumour volume and biomarker data with matched clinical information from 145 cases of EAC ethically overseen by the Northern Ireland Biobank were available for analysis. The diagnoses were made between 2004 to 2012.
A robust digital pathology workflow was used to quantify density of positive cells per mm2 of the initial tumour biopsy cores for the markers CD3, CD4, CD8 and CD45RO. High marker density was associated with better overall survival (OS) as judged by Kaplan Meier analysis.
Also in the discovery phase it was found that the immune checkpoint markers ICOS and PD-1 but not IDO-1 and PD-L1 were associated with significantly better OS by Kaplan Meier survival analysis.
Tumours expressing high CD3, CD4, CD8, CD45RO, ICOS, PD-1 and PD-L1 described as “immune hot” had five year survival rates of 74% compared to 11% in “immune cold” tumours with low levels of these markers. CD45RO and ICOS were independently prognostic in multivariate analysis including both markers. At high levels of these markers in the same cell there was a 65% survival rate over five years, but only 8% when both markers were low.
The study was limited to the stage of post-chemotherapy, which may alter the tumour profile compared to treatment naïve patients.
“In summary, we have identified a subpopulation of high CD45RO/ICOS EAC patients with significant positive prognostication. Moreover, these data provide evidence for the assessment of CD45RO/ICOS to be employed in the stratification of patients for clinical trials investigating the response to immunotherapy,” stated the authors.