Senbo Liu

As the latest and most anticipated method of tumor immunotherapy, CAR-NK therapy has received increasing attention in recent years, and its safety and high efficiency have irreplaceable advantages over CAR-T. Current research focuses on the application of CAR-NK in hematological tumors, while there are fewer studies on solid tumor. This article reviews the process of constructing CAR-NK, the effects of hypoxia and metabolic factors, NK cell surface receptors, cytokines, and exosomes on the efficacy of CAR-NK in solid tumor, and the role of CAR-NK in various solid tumor. The mechanism of action and the research status of the potential of CAR-NK in the treatment of solid tumor in clinical practice, and put forward the advantages, limitations and future problems of CAR-NK in the treatment of solid tumor.

Cancer immunotherapy has transformed traditional treatments, with immune checkpoint blockade being particularly prominent. However, immunotherapy has minimal benefit for patients in most types of cancer and is largely ineffective in some cancers (such as pancreatic cancer and glioma). A synergistic anti-tumor response may be produced through the combined application with traditional tumor treatment methods. Radiotherapy (RT) not only kills tumor cells but also triggers the pro-inflammatory molecules' release and immune cell infiltration, which remodel the tumor microenvironment (TME). Therefore, the combination of RT and immunotherapy is expected to achieve improved efficacy. In this review, we summarize the effects of RT on cellular components of the TME, including T cell receptor repertoires, different T cell subsets, metabolism, tumor-associated macrophages and other myeloid cells (dendritic cells, myeloid-derived suppressor cells, neutrophils and eosinophils). Meanwhile, non-cellular components such as lactate and extracellular vesicles are also elaborated. In addition, we discuss the impact of different RT modalities on tumor immunity and issues related to the clinical practice of combination therapy.

Abstract Cancer immunotherapy (CIT) has gained increasing attention and made promising progress in recent years, especially immune checkpoint inhibitors such as antibodies blocking programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). However, its therapeutic efficacy is only 10–30% in solid tumours and treatment sensitivity needs to be improved. The complex tissue environment in which cancers originate is known as the tumour microenvironment (TME) and the complicated and dynamic TME is correlated with the efficacy of immunotherapy. Ultrasound-targeted microbubble destruction (UTMD) is an emerging technology that integrates diagnosis and therapy, which has garnered much traction due to non-invasive, targeted drug delivery and gene transfection characteristics. UTMD has also been studied to remodel TME and improve the efficacy of CIT. In this review, we analyse the effects of UTMD on various components of TME, including CD8 + T cells, tumour-infiltrating myeloid cells, regulatory T cells, natural killer cells and tumour vasculature. Moreover, UTMD enhances the permeability of the blood-brain barrier to facilitate drug delivery, thus improving CIT efficacy in vivo animal experiments. Based on this, we highlight the potential of immunotherapy against various cancer species and the clinical application prospects of UTMD.