CD8A and nonpapillary renal cell carcinoma: In this study, we hypothesize that shikonin may be a beneficial combination partner for ipilimumab for the treatment of ccRCC patients due to its strong inhibitory effect on cancer stem cells, the significant reduction of FoxP3+ Treg cells in PBMC of patients and the activation of the endogenous effector CD3+CD8+ and CD3+CD4+ T cells in response to the recognition of tumor specific antigens.