Remarkable and Durable Tumor Response to Pembrolizumab in Locally Advanced dMMR/MSI-H Rectal Cancer

Anticancer Res. 2025 Nov;45(11):5069-5076. doi: 10.21873/anticanres.17847.

Abstract

Background/aim: Immune checkpoint inhibitors have demonstrated significant clinical efficacy in patients with mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer. Although current evidence is based on studies with limited sample sizes, recent findings suggest that anti-programmed cell death-1 (PD-1) antibodies are highly effective in patients with locally advanced dMMR/MSI-H rectal cancer.

Case report: We report the case of a 70-year-old man with locally advanced MSI-H rectal cancer who exhibited a remarkable and durable response to pembrolizumab. Histopathological examination revealed the infiltration of CD8-positive T lymphocytes and clusters of PD-L1-expressing macrophages within the tumor tissue. CD103-positive tissue-resident memory T-cells have also been identified in the tumor microenvironment, suggesting a robust and sustained local immune response.

Conclusion: Immune checkpoint blockade may represent a promising nonsurgical treatment option for patients with locally advanced dMMR/MSI-H rectal cancer.

Keywords: Rectal cancer; microsatellite instability-high; mismatch repair-deficient; pembrolizumab; tissue-resident memory T cells.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Agents, Immunological* / therapeutic use
  • DNA Mismatch Repair*
  • Humans
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Male
  • Microsatellite Instability*
  • Rectal Neoplasms* / drug therapy
  • Rectal Neoplasms* / genetics
  • Rectal Neoplasms* / immunology
  • Rectal Neoplasms* / pathology
  • Treatment Outcome
  • Tumor Microenvironment / drug effects

Substances

  • Antibodies, Monoclonal, Humanized
  • pembrolizumab
  • Antineoplastic Agents, Immunological
  • Immune Checkpoint Inhibitors