Immunoprofiling for Prognostic Assessment of Colon Cancer: a Novel Complement to Ultrastaging

Background: Although AJCC/TNM staging remains the gold standard for prognostic assessment of colon cancer, stage-specific outcomes vary. We therefore prospectively evaluated the prognostic role of immunoprofiling. Methods: Our cohort included 35 patients from an ongoing prospective trial of ultrastaging for colon cancer. Specimens were analyzed for T cell markers (CD3, CD4, CD8, and FoxP3). The number of tumor-infiltrating lymphocytes was analyzed at the tumor’s margin and center and correlated with AJCC/TNM stage, clinicopathologic variables, and disease-free survival. Results: There was a significant inverse association between number of CD3⁺ cells in the tumor center and tumor stage (P = 0.05). The tumor center/margin ratio of CD3⁺ cells also showed an inverse but non-significant relationship with nodal involvement (P = 0.07). Body mass index was inversely associated with numbers of CD3⁺(P = 0.04) and CD8⁺(P = 0.02) cells. Longer disease-free survival was correlated with higher CD8+ counts (P = 0.07), lower CD4⁺/CD8⁺ ratios (P = 0.008), and higher CD8⁺/FoxP3⁺ ratios (P = 0.02). Conclusions: This is the first prospective validation of immunoprofiling in patients whose colon cancer is staged with strict surgical and pathology quality measures. The apparent correlation between immunophenotypic response and clinical outcome warrants evaluation in a larger prospective trial.