Metabolic reprogramming allows tumor cells to prefer aerobic glycolysis as the main energy source, resulting in the massive accumulation of lactate in the tumor microenvironment (TME). It is found that lactate is no longer a waste product produced by glycolysis, but plays an important role in cancer progression. The modulation of lactate in the TME has become a promising target for cancer therapy. Although many small molecular inhibitors modulating the production or transport of lactate have appeared at present, their safety and efficacy have limited their further clinical application due to their non-specific targets and biodistribution. Studies have shown that nanomedicine has unique advantages, improving drug delivery efficiency and treatment efficacy while reducing damage to normal tissues, which greatly promotes the development of the research of nanosystems based on lactate modulation. In this review, we summarize the source and metabolism of lactate, the effect of lactate on the TME and recent advances in nanosystem-mediated strategies of lactate modulation for enhanced cancer therapy, hoping to provide ideas and directions for future research in related fields.

Immunotherapy techniques, such as immune checkpoint inhibitors, chimeric antigen receptor (CAR) T cell therapies and cancer vaccines, have been burgeoning with great success, particularly for specific cancer types. However, side effects with fatal risks, dysfunction in tumor microenvironment and low immune response rates remain the bottlenecks in immunotherapy. Nano metal-organic frameworks (nMOFs), with an accurate structure and a narrow size distribution, are emerging as a solution to these problems. In addition to their function of temporospatial delivery, a large library of their compositions, together with flexibility in chemical interaction and inherent immune efficacy, offers opportunities for various designs of nMOFs for immunotherapy. In this review, we overview state-of-the-art research on nMOFs-based immunotherapies as well as their combination with other therapies. We demonstrate that nMOFs are predominantly customized for vaccine delivery or tumor-microenvironment modulation. Finally, a prospect of nMOFs in cancer immunotherapy will be discussed.