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: 1.98). 02/2009; 8(3):231-9. DOI: 10.1007/s10689-009-9233-0
Source: PubMed


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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    ABSTRACT: High levels of microsatellite instability (MSI-high) are a cardinal feature of colorectal tumors from patients with Lynch Syndrome. Other key characteristics of Lynch Syndrome are that these patients experience fewer metastases and have enhanced survival when compared to patients diagnosed with microsatellite stable (MSS) colorectal cancer. Many of the characteristics associated with Lynch Syndrome including enhanced survival are also observed in patients with sporadic MSI-high colorectal cancer. In this review we will present the current state of knowledge regarding the mechanisms that are utilized by the host to control colorectal cancer in Lynch Syndrome and why these same mechanisms fail in MSS colorectal cancers.
    Full-text · Article · Jun 2010 · Clinical and Developmental Immunology

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    ABSTRACT: To review data demonstrating the prognostic and predictive impact of microsatellite instability (MSI) in human colon carcinomas. MSI is a molecular marker of defective DNA mismatch repair that is detected in approximately 15% of sporadic colon cancers. Most, but not all retrospective studies, have shown that colon cancers with MSI have better stage-adjusted survival rates compared with non-MSI tumors. Furthermore, analyses of colon cancers from participants in randomized adjuvant therapy trials have suggested that MSI tumors do not benefit from treatment with 5-fluorouracil. Recent studies, including a pooled analysis, validate prior data demonstrating the prognostic and predictive impact of MSI status in colon cancer. MSI is a molecular marker that can provide valuable prognostic and predictive information in colon cancer patients. In the appropriate clinical setting, MSI data can be used in clinical decision-making. Specifically, the favorable outcome of stage II colon cancers with MSI indicates that such patients should not receive adjuvant chemotherapy. Although data for stage III colon cancers with MSI suggest a lack of benefit from 5-fluorouracil alone, the benefit of the current standard treatment, 5-fluorouracil, leucovorin, and oxaliplatin, in this subgroup remains unknown and awaits further study.
    No preview · Article · Jun 2009 · Current opinion in oncology
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