Association between KSHV genotype and immune response to Kaposi sarcoma

Kaposi sarcoma (KS) is a locally aggressive endothelial tumor that can be classified into four clinical types: classic, AIDS-related, iatrogenic, and endemic. KS usually affects the skin and soft tissues, but it can develop into mucosal, lymph node, and multiple-organ lesions. KS is caused by Kaposi sarcoma-associated herpes virus (KSHV), which has six genotypes (A, B, C, D, E, and F). However, it remains unclear whether the KSHV genotype affects clinical presentation. In this study, we investigated clinical stage, cellular proliferation, NF-κB activity, and lymphocyte infiltration around the tumor of KS lesions. Additionally, we evaluated the association between the parameters described above and the viral genotypes. Classic KS with genotype C exhibited elevated proliferative activity and most cases progressed to an advanced stage. Lesions in classic KS with genotype C were limited to the skin with high CD4 and CD8 cell infiltration. In contrast, some AIDS-related KS patients with genotype A showed lymph node and visceral involvement and a lower number of immune cells around the tumor, which suggests that host immunity against KSHV affects the clinical presentation. Among patients with AIDS-related KS, the numbers of CD3 and CD8 cells in genotype C were higher than those in genotype A. These results imply that genotype C induces more potent host tumor immunity than genotype A. Thus, the present study suggests that the clinical presentation of KS is associated with both host immunity and KSHV genotypes.