Lactate dehydrogenase is crucial for tumor associated macrophage protection of multiple myeloma cells against chemotherapy

Multiple myeloma (MM) is a cancer characterized by an accumulation of malignant plasma cells in the bone marrow. Although chemotherapy is the most effective treatment, the majority of patients experience relapse. The major cause of treatment failure is the development of multidrug resistance. Thus, overcoming drug resistance will greatly improve patient survival. The enzyme lactate dehydrogenase (LDH) plays an important role in anaerobic respiration by converting pyruvate into lactate in the absence or low supply of oxygen. It has been observed that tumor-associated macrophages (TAMs) present in tumor environments can protect MM from chemotherapy treatment. We discovered that an LDH knockdown in myeloma cells decreased TAMs’ role in cell protection against chemotherapy treatment. Also, we found that, without LDH, macrophages were not able to differentiate into TAMs successfully. These results suggest that LDH activity in tumor environments promotes tumor survival, stimulates tumorigenesis, and manipulates local macrophages into performing pro-tumor functions