CD4 and plasma cell myeloma: It has been reported that advanced T-cell failure is associated with loss of cytotoxicity in CD4+ and CD8+ T cell subsets that produce IFN-γ, and early in vitro, studies have shown that IFN-γ directly inhibits myeloma cell growth, and preclinical models support a positive role for CD8+ T-cell failure in myeloma progression (88) (Figure 4).