CD4+ T-lymphocytopenia and systemic immune activation in patients with primary and secondary liver tumours

Using flow cytometry, we evaluated peripheral blood leucocyte subsets in 84 patients with primary and secondary liver cancer. The patients had significantly lower absolute (659+/-386 vs. 906+/-360 cells per microl, p=0.004) numbers of CD3+ CD4+, relative (9+/-5 vs. 12+/-4%, p=0.02) and absolute (154+/-115 vs. 221+/-83 cells per microl, p=0.02) numbers of CD8+ CD28+, absolute numbers of CD3+ and relative and absolute numbers of CD19+. Relative and absolute numbers of CD3+ DR+, CD3+ CD69+ and CD14+ CD16+ cells were significantly elevated in patients compared to controls. The phenotype was similar in 54 patients exposed to chemotherapy compared to 30 untreated patients. Urinary neopterin, a marker of systemic immune activation, was significantly higher in patients with liver tumours compared to controls. A negative correlation was observed between urinary neopterin and the absolute numbers of CD3+ CD4+ (Spearman rank correlation coefficient, rs = -0.54, p<0.0025) and CD19+ (rs = -0.49, p<0.01) in untreated patients. We conclude that, independently of prior chemotherapy, patients with liver present with markedly decreased numbers of CD3+ CD4+ lymphocytes as well as with other abnormalities of peripheral blood leukocyte phenotype. Similar to patients with human immunodeficiency virus infection, the decrease in CD3+ CD4+ lymphocytes is associated with systemic immune activation.