CD8+ lymphocytes/ tumour-budding index: an independent prognostic factor representing a ‘pro-/anti-tumour’ approach to tumour host interaction in colorectal cancer

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Abstract
The tumour-host interaction at the invasive front of colorectal cancer, including the epithelial–mesenchymal transition and its hallmark ‘tumour budding’, is an important area of investigation in terms of prognosis. The aim of this study was to determine the prognostic impact of a ‘pro-/anti-tumour’ approach defined by an established ‘pro-tumour’ (tumour budding) and host-related ‘anti-tumour’ factor of the adaptive immunological microenvironment (CD8+ lymphocytes). Double immunostaining for CK22/CD8 on whole tissue sections (n=279; Cohort 1) and immunohistochemistry for CD8+ using tissue microarrays (n=191; Cohort 2) was carried out. Tumour buds, CD8+ and CD8+ T-lymphocytes : tumour buds indices were evaluated per high-power field. In Cohort 1, a low-CD8+/ buds index was associated with lymph node metastasis (PP=0.009), worse survival in univariate (PPP=0.002). In Cohort 2, the CD8+/ buds index was associated with T stage (PP=0.041), vascular invasion (P=0.005) and survival in patients with TNM stage II (P=0.019), stage III (P=0.004), and adjuvantly untreated (P=0.009) and treated patients (P<0.001). The CD8+ lymphocyte : tumour-budding index is an independent prognostic factor in colorectal cancer and a promising approach for a future prognostic score for patients with this disease.