CD71+ erythroid cells promote multiple myeloma progression and impair anti-bacterial immune response.

Multiple myeloma (MM), one of the most frequent haematological malignancies, significantly increases the risk of bacterial infections due to treatment-related side effects, comorbidities and cancer-induced immune deficiencies. Recently, CD71+ erythroid cells (CECs) have been identified as key immunomodulators in neonates and cancer patients, but their role in MM progression remains unclear. Using a murine MM model, closely resembling human disease, we observed that MM progression is associated with anaemia and an increase in immature CECs, which are characterized by elevated arginase 2 (ARG2) expression. These MM-associated CECs suppress T-cell proliferation, contributing to impaired immune responses. Notably, ARG2 deficiency in mice led to slower MM progression and improved survival. Furthermore, MM-bearing mice exhibited higher susceptibility to Listeria monocytogenes infections, mirroring the increased infection risk in MM patients. Our findings suggest that ARG2-expressing CECs play a critical role in MM-associated immune suppression and infection susceptibility, pointing out ARG2 as a potential therapeutic target to enhance immune function and reduce infection risks in MM patients.