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. 2023 Feb 15;133(4):e167346. doi: 10.1172/JCI167346

Figure 1. TIGIT blockade synergizes with LEN maintenance to reduce immune escape in MM.

Figure 1

(A) The current standard of care for MM following ASCT involves maintenance with LEN treatment. However, most patients eventually relapse, and preclinical work suggests that immune dysfunction is a contributing factor to early relapse after ASCT. The study by Minnie et al. (5) discovered elevated levels of T cell exhaustion in mobilized peripheral blood stem cell grafts from patients with MM compared with healthy patients. Moreover, MM tumor cells may evade the immune system, in part, due to expression of the immune checkpoint TIGIT on effector memory (Tem) T cells and terminally differentiated effector memory T cells (Temra) in the bone marrow. (B) Antibodies that block TIGIT synergize with LEN maintenance by expanding polyfunctional T cells, including central memory T cells (Tcm), effector T cells (Teff), and exhausted T cells (Tex), in the bone marrow. Combination treatment in mice that includes TIGIT blockade with LEN maintenance limits T cell exhaustion, increases functional T cell accumulation in the bone marrow, and enhances durable anti-myeloma efficacy.