HAVCR2 and plasma cell myeloma: Key resistance mechanisms include: (a) chronic antigenic stimulation and upregulation of immune checkpoints (e.g., PD-L1, LAG-3, TIM-3, CTLA-4, TIGIT); (b) secretion of inhibitory cytokines (e.g., IL-10, IL-4, TGF-β, VEGF) that blunt anti-tumor immunity; (c) stromal cell mediated activation of pro-survival pathways and upregulation of antiapoptotic proteins and (d) the presence of myeloma stem-like cells which contribute to therapy failure [54].