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

被引:0
作者
Kristen M. Drescher
Poonam Sharma
Patrice Watson
Zoran Gatalica
Stephen N. Thibodeau
Henry T. Lynch
机构
[1] Creighton University School of Medicine,Department of Medical Microbiology and Immunology
[2] Creighton University School of Medicine,Department of Pathology
[3] Creighton University School of Medicine,Osteoporosis Research Center
[4] Department of Laboratory Medicine and Pathology,Department of Preventative Medicine
[5] Mayo Clinic,undefined
[6] Creighton University School of Medicine,undefined
来源
Familial Cancer | 2009年 / 8卷
关键词
Colorectal cancer; HNPCC; Lymphocytes; MSI high; T regs;
D O I
暂无
中图分类号
学科分类号
摘要
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.
引用
收藏
页码:231 / 239
页数:8
相关论文
共 244 条
[1]  
Jemal A(2004)Cancer statistics CA Cancer J Clin 54 8-29
[2]  
Thomas A(1999)Genetic susceptibility to nonpolyposis colorectal cancer J Med Genet 25 801-818
[3]  
Murray T(2003)Hereditary colorectal cancer N Eng J Med 348 919-932
[4]  
Thun M(1993)Microsatellite instability in cancer of the proximal colon Science 260 816-819
[5]  
Lynch HT(1993)Clues to the pathogenesis of familial colorectal cancer Science 260 812-816
[6]  
de la Chapelle A(1993)Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis Nature 363 558-561
[7]  
Lynch HT(2000)The prognostic significance of extensive microsatellite instability in sporadic clinicopathological stage C colorectal cancer Br J Surgery 87 1197-1202
[8]  
de la Chapelle A(2000)Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer N Eng J Med 342 69-77
[9]  
Thibodeau SN(2001)Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level Can Epidemiol Biomark Prev 10 917-923
[10]  
Bren G(1993)Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history Cancer Res 53 5849-5852