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
Deep Link:
http://www.dkfz.de/cgi-bin/sel?http://www.dkfz.de/PublicationManager/Show/ShowJournal.aspx%3fpublishedId=3382
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