2022

Elomaa, Hanna; Ahtiainen, Maarit; Väyrynen, Sara A.; Ogino, Shuji; Nowak, Jonathan A.; Friman, Marjukka; Helminen, Olli; Wirta, Erkki Ville; Seppälä, Toni T.; Böhm, Jan; Mäkinen, Markus J.; Mecklin, Jukka Pekka; Kuopio, Teijo; Väyrynen, Juha P.

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 colocalisation 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, Ptrend < 0.0001] and the validation cohort [adjusted HR for high (vs. low) 0.15, 95% CI 0.05–0.45, Ptrend < 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.