Tumor Infiltrating T Lymphocytes and Apoptosis in Colorectal Cancer.

Dysfunction of the immune system in colorectal cancer (CRC) can be due to a number of reasons including apoptosis of tumour infiltrating lymphocytes (TILs). The aims of this study was to investigate TILs in colorectal cancer and characterize apoptosis of TILs using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for detecting DNA fragments. We used monoclonal antibodies (mAbs) to T lymphocytes to detect TILs and double immunohistochemistry to assess apoptosis. T lymphocytes were detected in the immune infiltrate in CRC. TUNEL staining disclosed a high level of cell death among TILs. Apoptosis of T lymphocytes showed significant correlation with Dukes' stage (P = 0.02), lymphatic metastasis (P = 0.03), vascular metastasis (P = 0.01), lymph node metastasis (P = 0.02) and age of patient (P = 0.01). In conclusion, CRC may elude immunological surveillance by inducing apoptosis of TILs.

Apoptosis of T-cell subsets in colorectal cancer in vivo.

Dysfunction of the immune system in colorectal cancer (CRC) can be due to a number of reasons including apoptosis of tumour infiltrating lymphocytes (TILs). The aims of this study were to characterize, phenotypically, the apoptosis of TILs in CRC, and define the association of these findings with prognostic indicators. We used double immunohistochemistry to assess the apoptosis of T-cell subsets. Monoclonal antibodies to T lymphocytes, T helper cells, cytotoxic T cells (CTLs), natural killer cells (NK), CD45 and CD45RO were used. Antibodies against cleaved caspase-3 as a marker of apoptosis were used. Apoptosis of T-cell subsets was detected in the immune infiltrate in CRC. Apoptosis of T lymphocytes showed significant correlation with lymphatic metastasis (P = 0.01), Dukes' stage (P = 0.019). Apoptotic T helper cells showed significant correlation with metastasis (P = 0.04), lymphatic metastasis (P = 0.02), death (P = 0.04) and recurrence (P = 0.04). For apoptosis of CTLs, there was a significant correlation with histological classification (P = 0.02), lymphatic metastasis (P = 0.04), vascular metastasis (P = 0.03) and lymph node metastasis (P = 0.04). A significant association was found between the apoptosis of NK cells and the histological classification (P = 0.04). A significant association was found between the apoptosis of cd45RO cells and the histological classification (P = 0.04). In conclusion, apoptosis of lymphocytes provides theoretical foundation for metastasis and counterattack of colon cancer.

Hypoxia-induced EMAP-II transcription in colorectal cancer.

Endothelial monocyte-activating polypeptide-II (p431EMAP-II) is a proinflammatory cytokine and a chemoattractant for mononuclear phagocytes and polymorphonuclear leucocytes, found in culture supernatants of many tumour cell lines. It was demonstrated that p43/EMAP-II induces apoptosis in mitogen-stimulated lymphocytes, and suggested that it may be a constituent of a novel immune evasion mechanism employed by tumour cells. Quantitative real-time reverse transcription- polymerase chain reaction (qRT-PCR) analysis for EMAP-II mRNA was performed for colorectal adenocarcinoma cell lines, DLD-1, HT 29; human umbilical vein endothelial cells (HUVEC); and normal colon under normal and hypoxic conditions. Under hypoxic conditions, EMAP-II transcript expression increased up to 22-fold over normoxia in tumour cells, while there was 1-fold increase due to hypoxia in HUVEC and no increase in normal colon. These results demonstrate that EMAP-II transcripts are upregulated in tumour cells in hypoxic conditions and support the notion that EMAP-II plays a complex and important role in human cancer.