Intraepithelial CD8+ T-cell-count becomes a prognostic factor after a longer follow-up period in human colorectal carcinoma: possible association with suppression of micrometastasis

Abstract

T-cell infiltration into human cancer tissues can be a manifestation of host immune responses to cancer cells. The present study was undertaken to explore the clinicopathological significance of intraepithelial CD8 þ T cells using 371 consecutively sampled human colorectal carcinomas. By univariate analysis, we noted that the survival curves by intraepithelial CD8 þ T cells became separated only after 1 to 2 years postoperation. Multivariate analyses revealed that the beneficial effect of this factor becomes significant only after a longer (more than 2 year), but not after a shorter (less than 2 year) follow-up period. Furthermore, the number of intraepithelial CD8 þ T cells was significantly higher in patients alive for more than 5 years than in patients who either died of cancer after a curative operation or patients who underwent a noncurative operation. Patients' cancer-specific death long after a curative operation is thought to be caused by the growth of micrometastases in other organs or near the primary sites. The effects of intraepithelial CD8 þ T cells, therefore, may be mediated by suppression of micrometastasis, rather than suppression of growth in the primary tumour. In conclusion, our data support a hypothesis on the presence of systemic immunosurveillance against micrometastasis of cancer cells.

Evaluation of the prognostic value of systemic inflammation and socioeconomic deprivation in patients with resectable colorectal liver metastases

“…48 The prognostic value of lymphocytes does not appear to be reflected at the systemic level, however, as whilst the number of tumourinfiltrating CD8+ T-lymphocytes was found to correlate with patient outcome in primary CRC, the number of these cells in the systemic circulation showed no correlation with prognosis. 49,50 Similarly, a recent study found no correlation between total circulating lymphocyte count and outcome in patients with either operable primary CRC or unresectable CLM. 23 The findings of the current study are in line with these data.…”

A reversed CD4/CD8 ratio of tumor-infiltrating lymphocytes and a high percentage of CD4+FOXP3+ regulatory T cells are significantly associated with clinical outcome in squamous cell carcinoma of the cervix

“…31 observed that the presence of intratumoral CD8 1 T cells in cervical cancer was correlated with the lack of pelvic lymph node spread and was, therefore, correlated indirectly with prognosis. A high number of tumor-infiltrating CD8 1 T lymphocytes were observed as a favorable prognostic factor for survival in some studies of human cancers, including endometrial cancer, 32 ovarian cancer, 8 colorectal cancer, 33 esophageal cancer 34 and urothelial carcinoma. 35 Other studies on non-small cell lung cancer, 36 anal squamous cell carcinoma 24 and renal cell carcinoma 37 reported that CD8 1 T lymphocytes were a negative prognostic factor.…”

Immune Cells in Colorectal Cancer: Prognostic Relevance and Role of MSI

“…It has been postulated that MSI-H CRC are more immunogenic than microsatellite stable (MSS) tumors because of the generation of a large number of abnormal peptides by frameshift mutations [49,[65][66][67][68][69][70]. However, in the analysis of Chiba et al [52] there was no significant increase in the number of CD8 + IEL in cases with MSI. Therefore, it appears that although MSI could be associated with a high infiltration of T cells in tumor tissue, additional mechanisms like cross-priming of antigen-presenting cells by released intracellular antigens or the use of HLA class II machinery and T helper cell activity may provide an alternative pathway for immune stimulation in vivo [41,65,67].…”

“…However, while TILs might be expected to explain the increased apoptotic rate and improved prognosis of MSI-H cancers, it is likely that MSI-H cancers are intrinsically more prone to apoptosis, independently of T cell attack [73]. In addition, Buckowitz et al [74] and Chiba et al [52] suggested a protective role of functionally active lymphocytes directed against MSI-H CRCs, which may prevent tumor cell dissemination and metastasis formation in distant organs. Furthermore, it has been postulated that the abundance of CD8 + TILs found in MSI-H CRC might be due to the failure of these tumor cells to upregulateFasL.…”