Article

Lymphocyte recruitment into the tumor site is altered in patients with MSI-H colon cancer

Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.
Familial Cancer (Impact Factor: 1.62). 02/2009; 8(3):231-9. DOI: 10.1007/s10689-009-9233-0
Source: PubMed

ABSTRACT The ability of the host to mount an appropriate immune response to aberrant cells is one factor that determines prognosis in cancer patients. Naturally occurring regulatory T cells (T regs; CD4+ CD25+ cells) are key regulators of peripheral tolerance. It has been suggested that high levels of T regs are detrimental to the patient in some forms of cancer, but the role of these antigen-specific cells in individuals with colorectal cancers with high levels of microsatellite instability is unknown. Herein, we examined the ability of individuals with MSI-H or microsatellite stable colon cancer to recruit lymphocytes to the tumor site. Immunohistochemical staining was performed on archived paraffin-embedded specimens from a total of 38 individuals with MSI-H (n = 25) or MSS (n = 13) colon cancers to determine the proportion of CD3+, CD8+ and CD25+ cells infiltrating the tumor site. Patients with MSI-H colon cancers had increased percentages of CD8+ TILs (cytotoxic T cells) as compared to individuals with MSS colon cancer (47.3 vs. 24.04% of the infiltrate CD8+, respectively). No differences in the levels of CD25+ T cells were observed between individuals with MSI-H colon cancers and MSS colon cancers (0.53 vs. 0.54% CD25+, respectively). Together, these data suggest that the survival advantage enjoyed by patients with MSI-H colorectal cancer may, in part, be attributed to the increased cytolytic response, but not to an antigen-specific immunosuppressive response in MSS patients.

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    • "This particular study focused on patients with stage I and II CRC. Several studies have examined MSI-high colorectal carcinomas and characterized both the number and phenotype of the tumor infiltrating cells [30, 31, 41, 43, 47–49, 101, 102]. Studies by Smyrk et al. described an increased level of tumor infiltrating lymphocytes (TILs) in CRCs with high levels of microsatellite instability. "
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