High intratumoral CD8 positive T cell infiltration associated with pathologic complete response after neoadjuvant immunotherapy in locally advanced colon cancer

Neoadjuvant immunotherapy has shown high pathological response rates in mismatch repair-deficient (dMMR) locally advanced colon cancer. However, clinically applicable predictors of response remain insufficiently defined. We report three cases of patients with locally advanced mismatch repair-deficient (dMMR) colon cancer who received neoadjuvant immune checkpoint inhibitor (ICI) therapy (ipilimumab plus nivolumab or pembrolizumab) and subsequently underwent curative resection. All patients achieved a pathologic complete response (pCR). Pre-treatment biopsy specimens consistently demonstrated dense CD8+ T-cell infiltration on immunohistochemistry. Using a microscope field number of 22 at x400 magnification, the mean combined intraepithelial and stromal CD8+ T-cell densities were 244.1, 370.4, and 433.5 cells/mm2 in Case 1, Case 2, and the present case, respectively, suggesting a potential association between an immune-inflamed tumor microenvironment and favorable response to neoadjuvant immunotherapy. The findings of this case series support the feasibility and efficacy of neoadjuvant immunotherapy for locally advanced dMMR colon cancer. Dense CD8+ T-cell infiltration in pre-treatment biopsies may serve as a practical, low-cost, first-line biomarker for pCR; however, standardized quantitative thresholds and prospective validation are required before routine clinical application.