Discover oncology · 2026
High intratumoral CD8 positive T cell infiltration associated with pathologic complete response after neoadjuvant immunotherapy in locally advanced colon cancer.
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Okabayashi Hiroki, Teraishi Fuminori, Sumii Ryohei, Okamoto Koichi, Toyokawa Tatsuya, Omote Rika, Takahashi Ryusei, Utsumi Masashi, Miyaso Hideaki, Inagaki Masaru
Аннотация
BACKGROUND: 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.
CASE PRESENTATION: 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.
CONCLUSIONS: 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.
CASE PRESENTATION: 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.
CONCLUSIONS: 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.