Tumour‐infiltrating lymphocytes in colorectal cancer with microsatellite instability are activated and cytotoxic

Patients with colorectal cancer that display high‐level microsatellite instability (MSI‐H) appear to have a better prognosis. This may be explained by the pronounced T cell infiltrate seen in MSI‐H tumours that is related to a specific antigen‐driven immune response. The nature of tumour‐infiltrating lymphocytes in colorectal cancers was investigated using quantitative real‐time polymerase chain reaction (PCR) and immunohistochemistry.

[1]  B. Leggett,et al.  Tumour infiltrating lymphocytes and apoptosis are independent features in colorectal cancer stratified according to microsatellite instability status , 2001, Gut.

[2]  V. Moreno,et al.  Standardized approach for microsatellite instability detection in colorectal carcinomas. , 2000, Journal of the National Cancer Institute.

[3]  L. Aaltonen,et al.  Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history. , 1993, Cancer research.

[4]  W. Bodmer,et al.  Genetic steps in colorectal cancer , 1994, Nature Genetics.

[5]  J. Soares,et al.  BAT‐26 identifies sporadic colorectal cancers with mutator phenotype: a correlative study with clinico‐pathological features and mutations in mismatch repair genes , 1999, The Journal of pathology.

[6]  J. Scholefield,et al.  Increased activation of lymphocytes infiltrating primary colorectal cancers following immunisation with the anti-idiotypic monoclonal antibody 105AD7 , 1999, Gut.

[7]  A. House,et al.  Survival and the immune response in patients with carcinoma of the colorectum. , 1979, Gut.

[8]  F. Marincola,et al.  Inhibition of cytolytic T lymphocyte proliferation by autologous CD4+/CD25+ regulatory T cells in a colorectal carcinoma patient is mediated by transforming growth factor-beta. , 2002, Cancer research.

[9]  H Nagura,et al.  CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. , 1998, Cancer research.

[10]  J. Nesland,et al.  Frameshift-mutation-derived peptides as tumor-specific antigens in inherited and spontaneous colorectal cancer , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[11]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[12]  J. Jass Lymphocytic infiltration and survival in rectal cancer. , 1986, Journal of clinical pathology.

[13]  W. Bodmer,et al.  Immune surveillance in colorectal carcinoma , 1995, Nature Genetics.

[14]  D. Anderson,et al.  Leukocyte activation in the decidua of chromosomally normal and abnormal fetuses from women with recurrent abortion. , 2001, Human reproduction.

[15]  L. D. Tin,et al.  Microsatellite instability and high content of activated cytotoxic lymphocytes identify colon cancer patients with a favorable prognosis. , 2001, The American journal of pathology.

[16]  S. Bustin,et al.  Expression of HLA Class II in Colorectal Cancer: Evidence for Enhanced Immunogenicity of Microsatellite-Instability-Positive Tumours , 2001, Tumor Biology.

[17]  B J Bassam,et al.  Fast and sensitive silver staining of DNA in polyacrylamide gels. , 1991, Analytical biochemistry.

[18]  L. Aaltonen,et al.  Microsatellite instability is associated with tumors that characterize the hereditary non-polyposis colorectal carcinoma syndrome. , 1993, Cancer research.

[19]  Douglas G. Altman,et al.  Measurement in Medicine: The Analysis of Method Comparison Studies , 1983 .

[20]  Darryl Shibata,et al.  Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis , 1993, Nature.

[21]  R. Bleackley,et al.  Cytotoxic T lymphocytes: all roads lead to death , 2002, Nature Reviews Immunology.

[22]  R. Lothe,et al.  Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis , 2002, British Journal of Cancer.

[23]  A. Viel,et al.  High prevalence of activated intraepithelial cytotoxic T lymphocytes and increased neoplastic cell apoptosis in colorectal carcinomas with microsatellite instability. , 1999, The American journal of pathology.

[24]  J. Gebert,et al.  Microsatellite instability analysis: a multicenter study for reliability and quality control. , 1997, Cancer research.

[25]  S. Bustin Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays. , 2000, Journal of molecular endocrinology.

[26]  S Srivastava,et al.  A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. , 1998, Cancer research.

[27]  W. Bodmer,et al.  Selection for β2-microglobulin mutation in mismatch repair-defective colorectal carcinomas , 1996, Current Biology.

[28]  S N Thibodeau,et al.  Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. , 1998, Cancer research.

[29]  K. Kinzler,et al.  Clues to the pathogenesis of familial colorectal cancer. , 1993, Science.

[30]  M. Leppert,et al.  BAT-26 and BAT-40 instability in colorectal adenomas and carcinomas and germline polymorphisms. , 1999, The American journal of pathology.

[31]  G. Thomas,et al.  BAT-26, an indicator of the replication error phenotype in colorectal cancers and cell lines. , 1997, Cancer research.

[32]  A. House,et al.  Colonic carcinoma. A quantitative assessment of lymphocyte infiltration at the periphery of colonic tumors related to prognosis , 1978, Cancer.

[33]  B. Leggett,et al.  Prognostic significance of extensive microsatellite instability in sporadic clinicopathological stage C colorectal cancer , 2000, The British journal of surgery.

[34]  S. Bull,et al.  Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. , 2000, The New England journal of medicine.