Figure 1.

BM-resident CD69⁺ regulatory T cells (CD69⁺ Treg) decrease expression of CD39 which is required for the canonical CD39/CD73 adenosine pathway. This suggests that an alternative adenosine pathway involving ectoenzyme CD38, expressed on malignant plasma cells (PC), is active in the BM niches of NDMM patients. CD8⁺CD57⁺ terminal effector T cells (T_TE) originate from memory T cells (T_M) and may (1) undergo oligoclonal expansion into cytotoxic CD69^- T_TE (TCRVβ T_TE) with high expression of perforin and granzyme B, the ability to eliminate autologous PC in vitro and circulate between BM and PB or, (2) remain within the BM as non-cytotoxic BM-resident CD69⁺ T_TE with high inhibitory checkpoint expression (PD-1, TIGIT, Lag3, CD160) possibly promoted by BM-resident CD69⁺ Treg. Both CD69^- T_TE and BM-resident CD69⁺ T_TE produce large amounts of the inflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α). CD69⁻ T_TE and CD69⁺ T_TE establish an inverse relationship within the BM-resident T cell compartment of NDMM patients. Changes in Treg and CD69⁻ T_TE and CD69⁺ T_TE within the BM-resident T cell compartment of NDMM patients may be critical for myeloma surveillance at the site of disease initiation and progression.