Prognostic significance of spatial and density analysis of T lymphocytes in colorectal cancer
Hanna Elomaa, Maarit Ahtiainen, Sara A. Väyrynen, Shuji Ogino, Jonathan A. Nowak, Marjukka Friman, Olli Helminen, Erkki‐Ville Wirta, Toni T. Seppälä, Jan Böhm, Markus J. Mäkinen, Jukka‐Pekka Mecklin, Teijo Kuopio, Juha P. Väyrynen
Abstract
Abstract Background Although high T cell density is a strong favourable prognostic factor in colorectal cancer, the significance of the spatial distribution of T cells is incompletely understood. We aimed to evaluate the prognostic significance of tumour cell-T cell co-localisation and T cell densities. Methods We analysed CD3 and CD8 immunohistochemistry in a study cohort of 983 colorectal cancer patients and a validation cohort ( N = 246). Individual immune and tumour cells were identified to calculate T cell densities (to derive T cell density score) and G-cross function values, estimating the likelihood of tumour cells being co-located with T cells within 20 µm radius (to derive T cell proximity score). Results High T cell proximity score associated with longer cancer-specific survival in both the study cohort [adjusted HR for high (vs. low) 0.33, 95% CI 0.20–0.52, P trend < 0.0001] and the validation cohort [adjusted HR for high (vs. low) 0.15, 95% CI 0.05–0.45, P trend < 0.0001] and its prognostic value was independent of T cell density score. Conclusions The spatial point pattern analysis of tumour cell-T cell co-localisation could provide detailed information on colorectal cancer prognosis, supporting the value of spatial measurement of T cell infiltrates as a novel, robust tumour-immune biomarker.