The prognostic impact of tumor-infiltrating lymphocytes in colorectal cancer differs by anatomical subsite.
47 Background: Several studies report dense infiltration of tumour-infiltrating T cells and natural killer cells to be associated with an improved prognosis in colorectal cancer (CRC); but whether these associations differ by tumour location remain unknown. This study investigated the prognostic impact of immune cell infiltration in CRC, with particular reference to the anatomical subsite of the primary tumour. Methods: Immunohistochemical expression of CD3, CD8, FoxP3, and CD56 was analysed in tissue microarrays with tumours from 557 incident CRC cases from a prospective population-based cohort. Kaplan-Meier and Cox regression analyses were applied to determine the impact of biomarker expression on 5-year overall survival (OS), in the entire cohort and in subgroup analysis of right colon, left colon, and rectum. Results: In the entire cohort, dense infiltration of all the investigated immune cells correlated significantly with an improved 5-year OS in both univariable and multivariable analysis, adjusted for age, TNM stage, differentiation grade, and vascular invasion. Dense infiltration of CD3+ and CD8+ cells were independent favourable prognostic factors for tumours in the right colon (hazard ratio [HR] = 0.53, 95 % confidence interval [CI] 0.29-0.95 and HR = 0.35, 95% CI 0.19-0.65, respectively), but not in the left colon or rectum. When microsatellite instability status was included in the adjusted model, only CD8+ cells remained an independent favourable prognostic factor in right-sided tumours. Dense infiltration of FoxP3+ cells was an independent favourable prognostic factor for tumours in the rectum (HR = 0.54, 95% CI 0.30-0.99), but not in the right or left colon. Infiltration of CD56+ cells did not carry any independent prognostic impact after stratifying for primary tumour site. Conclusions: The results from this study demonstrate that the prognostic impact of certain T cell subsets in CRC differs by primary tumour site, being most evident in right-sided tumours. These findings indicate that tumour location may be an important factor to take into consideration in therapeutic decisions, including eligibility for immunotherapy.