Prognostic value of the CD4+/CD8+ ratio of tumour infiltrating lymphocytes in colorectal cancer and HLA-DR expression on tumour cells

Abstract

The purpose of this study was to clarify whether HLA-DR expression of colorectal tumour cells or the CD4+/CD8+ ratio of the tumour infiltrating lymphocytes is significantly associated with the prognosis of colorectal cancer. Using flow cytometry, we studied the tumour cell expression of the HLA class II in 70 enzymatically dissociated colorectal cancers and the phenotype of tumour infiltrating lymphocytes (TILs) in 41 cases. There was no trend in 5-year survival between three levels (low, medium, high) of HLA-DR expression on the tumour cells. Patients with low CD4+/CD8+ ratios had a better clinical course, with significantly higher 5-year survival, p=0.046, independent of the Dukes stage and age. Our results have implications for tumour immunology; colorectal cancer cells might be a target for cytotoxic T-lymphocytes, however the tumour cells are not able to initiate an immune response. Stimulation of the immune system could possible be obtained using dendritic cells cultured in vitro and loaded with tumour antigens.

Deficiency of the immunostimulatory cytokine IL-21 promotes intestinal neoplasia via dysregulation of the Th1/Th17 axis

“…A lower ratio represents a higher number of cytotoxic CD8 C T cells in relation to helper CD4 C T cells and has been correlated with a good prognosis in colorectal cancer. 22 Consistent with the hypothesis that IL-21 promotes a Th1 bias and favors antitumor immunity, in this model, the CD4 C /CD8 C T cell ratio was more than two times higher in the IL-21KO-APC MIN/C mice intestines as compared with that of APC MIN/C mice (Figs. 3B and C).…”

Invasive front of colorectal cancer: Dynamic interface ofpro-/anti-tumor factors

“…They found, by RT-PCR on 75 cases that mRNA levels of CD8, granzyme B and granulysin were significantly greater in patients without vascular emboli, lymphatic and perineural invasion (collectively known as VELIPI) compared to those with these features and that CD45RO+ cells had independent prognostic value [15] . Diederichsen et al [74] showed that a low CD4/CD8 ratio by flow cytometry was an independent prognostic factor for prolonged survival. In addition, Milasiene et al [75] evaluated inter-epithelial CD3, CD4, CD8, CD20 and CD16 and found that increased levels of all these markers, particularly of the natural killer cell marker CD16 led to significantly improved overall outcome [11,75] .…”

The effects of trastuzumab on the CD4+CD25+FoxP3+ and CD4+IL17A+ T-cell axis in patients with breast cancer

“…Several studies have shown that higher numbers of T-regulatory (T reg ) cells are associated with progression in a variety of malignancies, and T reg numbers appear increased in individuals with a variety of solid tumours (lung, breast and pancreas) and haematological malignancies, and this is reflected in the peripheral blood (PB) of cancer patients (Woo et al, 2001;Liyanage et al, 2002;Diederichsen et al, 2003;Javia and Rosenberg, 2003;Wolf et al, 2003;Marshall et al, 2004;Galon et al, 2006;Nedergaard et al, 2007). The T reg subgroup of immune cells suppresses the activity of effector cells, including CD4 þ and CD8 þ cytotoxic T cells, natural killer (NK) cells, dendritic cells, NK T (NKT) cells and B cells (Murakami et al, 2002;Trzonkowski et al, 2004).…”