Dominance of CD4+ alpha/beta T-cells and inferior role of innate immune reaction in liver metastases

BACKGROUND: Tumor infiltrating lymphocytes (TIL) are frequently present in human tumors with CD8+(-)T-cells as effector and CD4+ T-cells as helper cells. Despite the well established knowledge about primary tumors, only little is known about metastatic disease, especially for liver metastases. The role of the innate immune system in the tumor defence is still enigmatic. MATERIALS AND METHODS: We performed a subtyping of TIL in 20 liver metastases. Using immunohistochemistry, CD20+, CD3+, CD56+, CD4+ and CD8+ lymphocytes, gamma/delta-T-cells and alpha/beta-T-cells in the tumor, the peritumoral region, portal tracts and lobules were investigated. RESULTS: The immune response was highly accentuated in the surroundings of the metastases with only few lymphocytes in the tumor itself. There was a dominance of CD3+(-)CD4+(-)alpha/beta-T-cells with a lower number of CD8+(-)T-cells. The CD4+/CD8+ ratio was 6:1. CD56+(-)NK/NKT-cells and gamma/delta-T-cells were rare. No differences were found between metastases from different primaries or according to the number or diameter of the metastases. CONCLUSION: TIL are part of an interaction between the metastatic tumor and the liver. Among them CD4+ T-cells seem to have a unique independent function in tumor response. The localization of the immune response in the tumor periphery might be a reason for insufficient tumor defense. A defect in the innate immune system could be a reason for the escape of the metastatic tumor cells from tumor surveillance.