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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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  • 2
    Keywords: CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; radiotherapy ; SURVIVAL ; tumor ; TUMOR-CELLS ; AGENTS ; BLOOD ; CELL ; Germany ; THERAPY ; SAMPLE ; SAMPLES ; transcription ; PATIENT ; treatment ; bone marrow ; BONE-MARROW ; STAGE ; resistance ; colorectal cancer ; COLORECTAL-CANCER ; EFFICACY ; RATES ; chemotherapy ; CANCER-CELLS ; CANCER-PATIENTS ; CARCINOMAS ; CYTOKERATIN-20 ; POLYMERASE-CHAIN-REACTION ; adenocarcinoma ; BINARY ; ELIMINATION ; neoadjuvant treatment
    Abstract: Objective: To compare the detection rates for rectal cancer cells in blood and bone marrow in patients with or without preoperative chemoradiation.Summary Background Data: Previous reports have postulated a resistance of disseminated tumor cells to antiproliferative agents because of tumor cell dormancy.Methods: Blood samples from 142 patients (pre, intra-, and postoperative samples) and bone marrow samples from 127 patients undergoing resection of rectal adenocarcinoma were analyzed for tumor cells using a cytokeratin (CK) 20-reverse transcription polymerase chain reaction. The results were stratified according to preoperative therapy.Results: In patients without preoperative chemoradiation, tumor cell detection in blood and bone marrow correlated to tumor stage (Cochran Armitage trend test, P 〈 0.05). Tumor cells were detected in 34 of 103 (33%) bone marrow and 65 of 117 (55.6%) blood samples of patients without neoadjuvant treatment versus in 4 of 24 (16.7%) bone marrow and in 10 of 25 (40%) blood samples of patients with neoadjuvant treatment. The tumor cell detection rate was significantly lower in the group having undergone chemoradiation (binary logistic regression analysis, P 〈 0.05). The overall and disease-free survival were significantly worse in patients with tumor cell detection in the bone marrow after neoadjuvant therapy.Conclusions: Preoperative chemoradiation is associated with a decreased detection rate of rectal cancer cells in blood and bone marrow. These findings may explain the observed clinical benefit of patients with rectal cancer receiving chemoradiation. This is the first study suggesting that detection of disseminated rectal cancer cells may be useful for assessing the efficacy of neoadjuvant therapy
    Type of Publication: Journal article published
    PubMed ID: 14501498
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