Deep learning-based quantification of eosinophils and lymphocytes shows complementary prognostic effects in colorectal cancer patients

Abstract

The immune microenvironment of colorectal cancer is a major component of the disease and influences not only tumor progression and patient outcome but also therapy response. Expanding on existing studies which have explored the prognostic value of the adaptive immune response with lymphocytes, our study integrates innate immune cells, specifically eosinophils, in a combined analysis. To evaluate the prognostic significance of eosinophils within the context of lymphocyte infiltration, we analyzed a large collective of 1625 colorectal cancer cases from four different centers. For this purpose, we develop an automatic deep learning pipeline for quantification of these immune cells directly from hematoxylin and eosin-stained whole slide images. Our analysis shows eosinophils in the tumor front (EosF) as independent prognostic factor (HR = 0.70, 95%CI = 0.55 - 0.90, p = 0.005), particularly also in microsatellite instability (MSI) cases (HR = 0.32, 95%CI = 0.14 - 0.74, p = 0.008). Moreover, EosF and intraepithelial lymphocytes (IELs) counts are statistically independent and provide additive prognostic information (EosF: HR = 0.71, 95%CI = 0.55 - 0.90, p = 0.005, IELs HR = 0.59, 95%CI = 0.35 - 0.99, p = 0.047). Our study demonstrates that eosinophils are an independent prognostic factor, which can be automatically quantified, underscoring its high potential for translation to a diagnostic biomarker. Moreover, our work could pave the way towards an integrated immune score directly from hematoxylin and eosin-stained sections.