Prognostic role of tumour-infiltrating T lymphocytes in stage IIA (T3N0) colon cancer: A broad methodological study in a fairly homogeneous population.

Aim: Tumour-infiltrating T lymphocytes (TIL) are considered to be a reliable prognostic marker in CC, but the use in daily practice is unclear. We investigated the survival effect of TIL methodologically in a highly homogeneous population.

Methods: Seventy-two stage IIA (T3N0) CC patients who underwent surgical resection from 2000 to 2014 were included. CD3 and CD8 were separately scored for different blocks, areas and foci. To the best of our knowledge, this study has the most comprehensive methodology in the literature.

Results: Foremost, we searched for the optimal evaluation method. We found better results with Model A (deepest invasive block&hot spot area&invasive margin focus), e.g. for CD3, the relationship with prognostic factors [Crohn's-like reaction (p = 0.015), positive surgical margin (p = 0.019), Mismatch repair proteins deficiency (p = 0.003), advanced grade (p = 0.015)], the correlation of distinct estimates (r = 0.708), the reproducibility of research (Κappa = 0.60-0.71), and the usefulness of cut-off value (area of under ROC = 0.800 [0.683-0.917]) were best. Then, survival analysis was performed with two better methods including Model A. In univariate analysis, low TIL with Model A was associated with worse OS (CD3, p < 0.001; CD8, p = 0.023) and RFS (CD3, p < 0.001; CD8, p = 0.005). Multivariate analyses confirmed low TIL with same method as an independent worse prognostic marker for OS (CD3, Hazard ratio [HR] = 1.42 [1.10-1.85], p = 0.005) and RFS (CD3, HR = 1.46 [1.17-1.83], p = 0.001; CD8, HR = 1.32 [1.05-1.64], p = 0.032).

Conclusions: Our results confirm that low TIL is an independent worse prognostic marker in stage IIA (T3N0) CC and that the use of CD3 with Model A can contribute to improving the prognostication of early CCs.