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    Keywords: CANCER ; CELLS ; EXPRESSION ; tumor ; BLOOD ; carcinoma ; CELL ; Germany ; QUANTIFICATION ; TISSUE ; TIME ; PATIENT ; ACTIVATION ; RESPONSES ; IFN-GAMMA ; prognosis ; ANTIGEN ; T cell ; T cells ; T-CELL ; T-CELLS ; MOLECULE ; bone marrow ; BONE-MARROW ; BREAST-CANCER ; IMMUNE-RESPONSES ; STAGE ; IN-SITU ; immunohistochemistry ; NUMBER ; colorectal cancer ; COLORECTAL-CANCER ; LYMPHOCYTES ; microsatellite instability ; MIGRATION ; CANCER-PATIENTS ; IMMUNE-RESPONSE ; T-LYMPHOCYTES ; FLUORESCENCE ; CANCER PATIENTS ; T lymphocytes ; INFILTRATION ; PROGNOSTIC-FACTOR ; IMMUNE-SYSTEM ; TUMOR TISSUE ; T helper cell ; correlation ; T helper cells ; BONE ; CD8(+) T cell ; immune responses ; CELL RESPONSE
    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. Summary Background Data: 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
    Type of Publication: Journal article published
    PubMed ID: 17122624
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