Lymphocyte recruitment into the tumor site is altered in patients with MSI-H colon cancer.
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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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.Current opinion in oncology 06/2009; 21(4):369-73. DOI:10.1097/CCO.0b013e32832c94bd · 3.76 Impact Factor
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ABSTRACT: Tumor-host interaction at the invasive front of colorectal cancer represents a critical interface encompassing a dynamic process of de-differentiation of colorectal carcinoma cells known as epithelial mesenchymal transition (EMT). EMT can be identified histologically by the presence of "tumor budding", a feature which can be highly specific for tumors showing an infiltrating tumor growth pattern. Importantly, tumor budding and tumor border configuration have generated considerable interest as additional prognostic factors and are also recognized as such by the International Union Against Cancer. Evidence seems to suggest that the presence of tumor budding or an infiltrating growth pattern is inversely correlated with the presence of immune and inflammatory responses at the invasive tumor front. In fact, several tumor-associated antigens such as CD3, CD4, CD8, CD20, Granzyme B, FOXP3 and other immunological or inflammatory cell types have been identified as potentially prognostic in patients with this disease. Evidence seems to suggest that the balance between pro-tumor (including budding and infiltrating growth pattern) and anti-tumor (immune response or certain inflammatory cell types) factors at the invasive front of colorectal cancer may be decisive in determining tumor progression and the clinical outcome of patients with colorectal cancer. On one hand, the infiltrating tumor border configuration and tumor budding promote progression and dissemination of tumor cells by penetrating the vascular and lymphatic vessels. On the other, the host attempts to fend off this attack by mounting an immune response to protect vascular and lymphatic channels from invasion by tumor buds. Whereas standard pathology reporting of breast and prostate cancer involves additional prognostic features, such as the BRE and Gleason scores, the ratio of pro- and anti-tumor factors could be a promising approach for the future development of a prognostic score for patients with colorectal cancer which could complement tumor node metastasis staging to improve the clinical management of patients with this disease.World Journal of Gastroenterology 12/2009; 15(47):5898-906. DOI:10.3748/wjg.15.5898 · 2.43 Impact Factor