Tumour-infiltrating lymphocytes in colorectal cancer with microsatellite instability are activated and cytotoxic

Br J Surg. 2004 Apr;91(4):469-75. doi: 10.1002/bjs.4472.


Background: Patients with colorectal cancer that display high-level microsatellite instability (MSI-H) appear to have a better prognosis. This may be explained by the pronounced T cell infiltrate seen in MSI-H tumours that is related to a specific antigen-driven immune response. The nature of tumour-infiltrating lymphocytes in colorectal cancers was investigated using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry.

Methods: Quantitative fluorescent hydrolysis probe-based reverse transcriptase-PCR assays were used to detect levels of mRNA specifying T cell markers in fresh frozen colorectal tissue from MSI-H tumours and those with little or no microsatellite instability (microsatellite stable (MSS) tumours). In addition, immunohistochemistry was performed on paraffin-embedded sections to compare expression of the same T cell markers and the activation markers granzyme B and interleukin 2 receptor alpha-subunit (IL-2Ralpha) in MSI-H and MSS tumours.

Results: MSI-H tumours contained higher ratios of CD8/CD3 mRNA copy numbers than MSS tumours (P = 0.016), confirming the cytotoxic nature of lymphocyte infiltrates in this subset of colorectal cancers. Furthermore, immunohistochemistry confirmed that MSI-H tumours contained more infiltrating lymphocytes than MSS tumours, as shown by increased expression of CD3 (P = 0.003) and CD8 (P = 0.008). Consistent with other studies, the lymphocytes in MSI-H tumours were activated as indicated by significantly higher granzyme B counts (P = 0.020) and a significantly higher level of expression of IL-2Ralpha (P = 0.017).

Conclusion: The results support the hypothesis that MSI-H colorectal cancers may be more immunogenic than MSS tumours.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • CD3 Complex / immunology
  • CD8 Antigens / immunology
  • Colorectal Neoplasms / immunology*
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Microsatellite Repeats / immunology*
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction / methods


  • CD3 Complex
  • CD8 Antigens