The inhibitory receptor PVRIG is dominantly expressed in the bone marrow of patients with multiple myeloma and its blockade enhances T-cell engager's immune activation

•PVRIG is highly expressed in various T-cell populations, including NK and NKT cells•PVRIG blockade might contribute to a positive clinical outcome in MM patients•PVRIG blockade, in combination with BiTE, enhances T-cell activation in MM BM Therapeutic advances in treating patients with multiple myeloma (MM), including novel immunotherapies, have improved the disease control, but it remains incurable. Although traditional immune check point inhibitors have shown limited clinical benefit, targeting alternative immune-inhibitory pathways may offer a novel way to address relapsed disease. Blockade of the immune regulator TIGIT was shown to enhance anti-tumor immunity in preclinical MM models. Beyond TIGIT, the DNAM-1 axis includes the novel inhibitory receptor PVRIG. In this study we evaluated the expression of DNAM-1 axis receptors and the function of PVRIG in bone marrow of individuals with MM, specifically highlighting PVRIG blockade as a potential therapeutic opportunity in combination with bi-specific T-cell engager (BiTE).