title: 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.
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA. kdresche@creighton.edu
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Drescher
authors.forename: Poonam
authors.initials: P
authors.lastname: Sharma
authors.forename: Patrice
authors.initials: P
authors.lastname: Watson
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gatalica
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
mesh_terms: D017209:Apoptosis; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000235:genetics*; D004260:DNA Repair; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D053842:Microsatellite Instability; D013388:Succinimides / Q000097:blood* / Q000276:immunology / Q000652:urine; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: C110990:N-methylsuccinimide; D013388:Succinimides