Abstract
An immune cell score (ICS) was introduced for predicting survival in pancreatic ductal adenocarcinoma (PDAC). Few studies have compared different methods of evaluating immune infiltrate. This study compared ICSs determined in whole sections or tissue microarray-like hotspots for predicting survival after PDAC surgery. We included in 79 consecutive patients from a single geographical area that underwent surgery for PDAC (R0/R1, stages I–III). We performed digital image analyses to evaluate CD3 and CD8 staining. ICSs were classified as low, moderate, or high, based on the numbers of immune cells in the tumour core and invasive margin. We compared ICS groups determined with the hotspot and whole-section techniques. Associations between ICS and survival were analysed with Cox regression models, adjusted for sex, age, tumour stage, differentiation grade, perineural invasion, and resection radicality. In hotspot ICS analysis, 5-year overall survival rates for low, moderate, and high groups were 12.1%, 26.3%, and 26.8%, respectively (p = 0.193). In whole-section analyses, overall survival rates were 5.3%, 26.4%, and 43.8%, respectively (p = 0.030). In the adjusted Cox model, whole-section ICS groups were inversely associated with the overall mortality hazard ratio (HR): low, moderate, and high ICS groups had HRs of 1.00, 0.42 (95% CI 0.20–0.88), and 0.27 (95% CI 0.11–0.67), respectively. The number of immune cells per square millimetre in the tumour core and the invasive margin were significantly higher and had a wider range in hotspots than in whole-tissue sections. Accordingly, ICS could predict survival in patients with PDAC after surgery. Whole tissue section ICSs exhibited better prognostic value than hotspot ICSs.
Highlights
Cancer progression is known to be strongly influenced by the host immune response, which is represented by immune cell infiltrates [1, 2]
When we compared the numbers of immune cells between whole sections and hotspots, we found that the median number of immune cells per square millimetre was significantly higher in hotspots than in whole tissue sections
Our analyses suggested that the whole-section technique was superior to the tissue microarrays (TMAs)-like hotspot technique
Summary
Cancer progression is known to be strongly influenced by the host immune response, which is represented by immune cell infiltrates [1, 2]. Multiple scoring systems have been developed to evaluate the association between the host immune response and survival of patients with. TNM staging ignores the impact of the host immune response. It has been shown that tumour-infiltrating lymphocytes were correlated with survival in rectal, oesophageal, and gastric cancers [8,9,10]. In colorectal cancer, a computer-assisted evaluation of the quantity of CD3+ and CD8+ lymphocytes, known as the Immunoscore®, was found to be a reproducible, independent prognostic parameter [11]. It was suggested that integrating the TNM and Immunoscore® might provide more accurate staging
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