Prognostic significance of spatial and density analysis of T lymphocytes in colorectal cancer

• Published in: British journal of cancer Vol. 127; no. 3; pp. 514 - 523
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-08-2022; Nature Publishing Group
• Subjects: 631/67/580; 692/4028/67/1504/1885; 692/4028/67/327; Biomarkers, Tumor - analysis; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; CD3 antigen; CD8 antigen; CD8-Positive T-Lymphocytes; Cell density; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - pathology; Drug Resistance; Epidemiology; Humans; Immunohistochemistry; Localization; Lymphocyte Count; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating; Medical prognosis; Molecular Medicine; Oncology; Prognosis; Spatial distribution; T-Lymphocytes - pathology; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-022-01822-6

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.