Activation of immune signals during organ transplantation

The activation of host’s innate and adaptive immune systems can lead to acute and chronic graft rejection,which seriously impacts graft survival.Thus,it is particularly significant to clarify the immune signals,which are critical to the initiation and maintenance of rejection generated after transplantation.The initiation of response to graft is dependent on sensing of danger and stranger molecules.The ischemia and reperfusion of grafts lead to cell stress or death,followed by releasing a variety of damage-associated molecular patterns(DAMPs),which are recognized by pattern recognition receptors(PRRs)of host immune cells to activate intracellular immune signals and induce sterile inflammation.In addition to DAMPs,the graft exposed to‘non-self’antigens(stranger molecules)are recognized by the host immune system,stimulating a more intense immune response and further aggravating the graft damage.The polymorphism of MHC genes between different individuals is the key for host or donor immune cells to identify heterologous‘non-self’components in allogeneic and xenogeneic organ transplantation.The recognition of‘nonself’antigen by immune cells mediates the activation of immune signals between donor and host,resulting in adaptive memory immunity and innate trained immunity to the graft,which poses a challenge to the long-term survival of the graft.This review focuses on innate and adaptive immune cells receptor recognition of damage-associated molecular patterns,alloantigens and xenoantigens,which is described as danger model and stranger model.In this review,we also discuss the innate trained immunity in organ transplantation.

Targeting macrophage metabolism to enhance tumor immunotherapy

Tumor-associated macrophages(TAMs)are important components of the tumor microenvironment(TME)and are characterized by plasticity and heterogeneity.This heterogeneity reflects the ability of macrophages to respond to environmental stimuli,leading to their differentiation from proinflammatory(M1-like)to anti-inflammatory(M2-like)phenotypes[1].Specific subsets of TAMs mediate different processes,such as orchestrating angiogenesis,extracellular matrix remodeling,cancer cell proliferation,metastasis,and immunosuppression,by providing malignant cells with trophic and nutrient support,which is mostly related to poorer clinical outcomes[2,3].Moreover,TAMs mediate tumor phagocytosis and promote antitumor immunity,leading to better clinical outcomes.Thus,how to regulate TAMs to reverse their transition from the M2-like phenotype to the M1-like phenotype is an urgent scientific issue.