title: Tumor infiltrating T lymphocytes in colorectal cancer: Tumor-selective activation and cytotoxic activity in situ.
abstract: OBJECTIVE
  To examine whether tumor-selective infiltration, activation, and cytotoxic activity of tumor infiltrating T lymphocytes (TIL) can be demonstrated in situ in colorectal cancer samples.
  
  
  BACKGROUND
  Recent studies indicated a correlation between the presence of TIL and an improved prognosis in colorectal cancer. However, tumor-selective activation and cytotoxic activity of CD8 TIL in situ in colorectal cancer patients have not yet been examined.
  
  
  METHODS
  Tumor samples from 49 patients and corresponding normal mucosa samples from 23 patients with colorectal cancer (UICC stages II-IV) were examined for TIL. Two-color fluorescence immunohistochemistry and multicolor flowcytometric (FACS) analysis were used for quantification of CD8 T cells and measurement of their activation status (CD69-expression) and cytotoxic activity (CD107a-expression) in situ. Presence of tumor antigen-reactive T cells in tumor, blood, and bone marrow was evaluated by IFN-gamma Elispot analysis.
  
  
  RESULTS
  While absolute numbers of CD8 T cells were similar, CD4 T helper cells were significantly increased in tumor tissue compared with normal mucosa. There was a significantly higher proportion of activated and cytotoxically active CD8 TIL in colorectal cancer compared with normal mucosa. Increased activation, cytotoxic activity, and functional reactivity of TIL were correlated with the presence of functional tumor antigen-reactive T cells in the blood and bone marrow. The proportion of activated TIL decreased significantly with higher tumor stage.
  
  
  CONCLUSIONS
  Tumor-selective activation and cytotoxic activity of CD8 TIL and tumor-selective migration of CD4 T helper cells were demonstrated in colorectal cancer for the first time. Our data support the immunogenicity of colorectal cancer and suggest clinical significance of tumor-specific immune responses.
authors.affiliation: Department of Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Koch
authors.forename: Philipp
authors.initials: P
authors.lastname: Beckhove
authors.forename: Jan
authors.initials: J
authors.lastname: Op den Winkel
authors.forename: Daniel
authors.initials: D
authors.lastname: Autenrieth
authors.forename: Philipp
authors.initials: P
authors.lastname: Wagner
authors.forename: Daniel
authors.initials: D
authors.lastname: Nummer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Specht
authors.forename: Dalibor
authors.initials: D
authors.lastname: Antolovic
authors.forename: Luis
authors.initials: L
authors.lastname: Galindo
authors.forename: Friedrich H
authors.initials: FH
authors.lastname: Schmitz-Winnenthal
authors.forename: Volker
authors.initials: V
authors.lastname: Schirrmacher
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Jürgen
authors.initials: J
authors.lastname: Weitz
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000502:physiology*; D008297:Male; D009367:Neoplasm Staging
chemical_list: D015703:Antigens, CD