The recent successes of tumor immunotherapy approaches, such as immune checkpoint blockade (ICB) and chimeric antigen receptor T cell (CAR-T) therapy, have revolutionized cancer treatment, improving efficacy and extending treatment to a larger proportion of cancer patients. However, due to high heterogeneity of cancer, poor tumor cell targeting, and the immunosuppressive status of the tumor microenvironment (TME), combinatorial agents are required to obtain more effective and consistent therapeutic responses in a wide range of cancers. Oncolytic viruses (OVs) are able to selectively replicate in and destroy tumor cells and subsequently induce systematic anti-tumor immune responses. Thus, they are ideal for combining with cancer immunotherapy. In this review, we discuss the current understanding of OVs, as well as the latest preclinical and clinical progress of combining OVs with cancer immunotherapies, including ICB, CART therapy, bispecific T cell engagers (BiTEs), and cancer vaccines. Moreover, we consider future directions for applying OVs to personalized cancer immunotherapies, which could potentially launch a new generation of cancer treatments.

Pathogenic factors driving obesity to type 2 diabetes (T2D) are not fully understood. Group 1 innate lymphoid cells (ILC1s) are effectors of innate immunity and enriched in inflamed tissues. Here we show that the number of adipose ILC1s increases in obese T2D patients and correlates with glycemic parameters and with the number of ILC1s in the blood; circulating ILC1 numbers decrease as a result of metabolic improvements after bariatric surgery. In vitro co-culture experiments show that human adipose ILC1s promote adipose fibrogenesis and CD11c + macrophage activation. Reconstruction of the adipose ILC1 population in Prkdc −/− IL2rg −/− mice by adoptive transfer drives adipose fibrogenesis through activation of TGFβ1 signaling; however, transfer of Ifng −/− ILC1s has no effect on adipose fibrogenesis. Furthermore, inhibiting adipose accumulation of ILC1s using IL-12 neutralizing antibodies attenuates adipose tissue fibrosis and improves glycemic tolerance. Our data present insights into the mechanisms of local immune disturbances in obesity-related T2D.

The ability of nanomotors to promote the deep penetration of themselves and the loaded drugs in diseased tissues has been proposed and confirmed. However, whether such motion behavior of the nanomotors can also promote deep penetration of micrometer-sized immune cells in the diseased microenvironment, which is important for the immunotherapy of some diseases, has not been mentioned. Herein, we construct a nitric oxide (NO)-driven nanomotor that can move in the tumor microenvironment, focusing on its motion behavior and the role of NO, the beneficial product released during movement from this kind of nanomotor, in regulating the infiltration behavior and activity of immune cells. It can be found that the drug-loaded nanomotors with both NO-releasing ability and motility can promote the normalization of the tumor vasculature system and the degradation of the intrinsic extracellular matrix (ECM), which can significantly improve the tumor infiltration ability of T cells in vivo. The efficiency of T-cell infiltration in tumor tissue in vivo increased from 2.1 to 28.2%. Both subcutaneous and intraperitoneal implantation tumor models can validate the excellent antitumor effect of drug-loaded NO-driven nanomotors. This combination of motility of the power source from nanomotors and their physiological function offers a design idea for therapeutic agents for the future immunotherapy of many diseases.

Emerging evidence highlights that dysfunction of adipose tissue contributes to impaired insulin sensitivity and systemic metabolic deterioration in obese state. Of note, adipocyte hypertrophy serves as a critical event which associates closely with adipose dysfunction. An increase in cell size exacerbates hypoxia and inflammation as well as excessive collagen deposition, finally leading to metabolic dysregulation. Specific mechanisms of adipocyte hypertrophy include dysregulated differentiation and maturation of preadipocytes, enlargement of lipid droplets, and abnormal adipocyte osmolarity sensors. Also, weight loss therapies exert profound influence on adipocyte size. Here, we summarize the critical role of adipocyte hypertrophy in the development of metabolic disturbances. Future studies are required to establish a standard criterion of size measurement to better clarify the impact of adipocyte hypertrophy on changes in metabolic homeostasis.