Advances in metabolic reprogramming of NK cells in the tumor microenvironment on the impact of NK therapy.

Natural killer (NK) cells are unique from other immune cells in that they can rapidly kill multiple neighboring cells without the need for antigenic pre-sensitization once the cells display surface markers associated with oncogenic transformation. Given the dynamic role of NK cells in tumor surveillance, NK cell-based immunotherapy is rapidly becoming a "new force" in tumor immunotherapy. However, challenges remain in the use of NK cell immunotherapy in the treatment of solid tumors. Many metabolic features of the tumor microenvironment (TME) of solid tumors, including oxygen and nutrient (e.g., glucose, amino acids) deprivation, accumulation of specific metabolites (e.g., lactate, adenosine), and limited availability of signaling molecules that allow for metabolic reorganization, multifactorial shaping of the immune-suppressing TME impairs tumor-infiltrating NK cell function. This becomes a key barrier limiting the success of NK cell immunotherapy in solid tumors. Restoration of endogenous NK cells in the TME or overt transfer of functionally improved NK cells holds great promise in cancer therapy. In this paper, we summarize the metabolic biology of NK cells, discuss the effects of TME on NK cell metabolism and effector functions, and review emerging strategies for targeting metabolism-improved NK cell immunotherapy in the TME to circumvent these barriers to achieve superior efficacy of NK cell immunotherapy.

Research progress on the role of tumor­associated macrophages in tumor development and their use as molecular targets (Review).

The tumor microenvironment (TME) is a complex system composed mainly of tumor cells, mesenchymal cells and immune cells. Macrophages, also known as tumor­associated macrophages (TAMs), among innate immune cells, are some of the most abundant components of the TME. They may influence tumor growth and metastasis through interactions with other cell populations in the TME and have been associated with poor prognosis in a variety of tumors. Therefore, a better understanding of the role of TAMs in the TME may provide new insight into tumor therapy. In the present review, the origin and classification of TAMs in the TME were outlined and their polarization and dual effects on tumor cells, as well as emerging strategies for cancer therapies targeting TAMs, were discussed.

Bufalin serves as a pharmaceutic that mitigates drug resistance.

Intrinsic or acquired drug resistance of tumor cells is the main cause of tumor chemotherapy failure and tumor-related death. Bufalin (BF) is the main active monomer component extracted from the Traditional Chinese Medicine Toad venom (secretions of glands behind the ears and epidermis of bufo gargarizans and Bufo Melanostictus Schneider). It is a cardiotonic steroid with broad-spectrum anti-cancer effects and has been widely used against various malignant tumors in clinical practice. Pharmacological studies also found that BF has the effect of reversing drug resistance, which provides a new perspective for the application of Traditional Chinese Medicine as a chemosensitizer in cancer therapy. This article provides an extensive search and summary of published research on mitigating drug resistance to BF and reviews its potential mechanisms.