ABSTRACT
[This corrects the article DOI: 10.1016/j.apsb.2023.04.002.].
ABSTRACT
Tumors in which the microenvironment is characterized by lack of immune cell infiltration are referred as "cold tumors" and typically exhibit low responsiveness to immune therapy. Targeting the factors contributing to "cold tumors" formation and converting them into "hot tumors" is a novel strategy for improving the efficacy of immunotherapy. Adenosine, a hydrolysis product of ATP, accumulates with a significantly higher concentration in the tumor microenvironments compared with normal tissue and exerts inhibitory effects on tumor-specific adaptive immunity. Tumor cells, dendritic cells, macrophages, and T cells express abundant adenosine receptors on their surfaces. The binding of adenosine to these receptors initiates downstream signaling pathways that suppress tumor antigen presentation and immune cell activation, consequently dampening adaptive immune responses against tumors. Adenosine down-regulates the expression of major histocompatibility complex Ⅱ and co-stimulatory factors on dendritic cells and macrophages, thereby inhibiting antigen presentation to T cells. Adenosine also inhibits ligand-receptor binding and transmembrane signaling on T cells, concomitantly suppressing the secretion of anti-tumor cytokines and impairing T cell activation. Furthermore, adenosine hinders effector T cell trafficking to tumor sites and infiltration by inhibiting chemokine secretion and KCa3.1 channels. Additionally, adenosine promotes the secretion of immunosuppressive cytokines, increases immune checkpoint protein expression, and enhances the activity of immunosuppressive cells, collectively curbing cytotoxic T cell-mediated tumor cell killing. Given the immunosuppressive role of adenosine in adaptive antitumor immunity, several inhibitors targeting adenosine generation or adenosine receptor blockade are currently in preclinical or clinical development with the aim of enhancing the effectiveness of immunotherapies. This review provides an overview of the inhibitory effects of adenosine on adaptive antitumor immunity, elucidate the molecular mechanisms involved, and summarizes the latest advances in application of adenosine inhibition strategies for antitumor immunotherapy.
Subject(s)
Humans , Adenosine/pharmacology , T-Lymphocytes , Adaptive Immunity , Cytokines , Neoplasms/therapy , Tumor MicroenvironmentABSTRACT
Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8+ T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.
ABSTRACT
Immunotherapy strategies targeting the programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) pathway in clinical treatments have achieved remarkable success in treating multiple types of cancer. However, owing to the heterogeneity of tumors and individual immune systems, PD-L1/PD-1 blockade still shows slow response rates in controlling malignancies in many patients. Accumulating evidence has shown that an effective response to anti-PD-L1/anti-PD-1 therapy requires establishing an integrated immune cycle. Damage in any step of the immune cycle is one of the most important causes of immunotherapy failure. Impairments in the immune cycle can be restored by epigenetic modification, including reprogramming the environment of tumor-associated immunity, eliciting an immune response by increasing the presentation of tumor antigens, and by regulating T cell trafficking and reactivation. Thus, a rational combination of PD-L1/PD-1 blockade and epigenetic agents may offer great potential to retrain the immune system and to improve clinical outcomes of checkpoint blockade therapy.
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Objective To discuss the effective nursing measures in interventional therapy for deep vein thrombosis (DVT) of lower extremities in order to improve the successful rate of the procedure and to decrease the occurrence of complications. Methods Comprehensive nursing measures, including general nursing care, specific nursing care and emergency nursing care, were employed in 63 DVT patients receiving interventional therapy. Clinical response and complications were observed. Results After the treatment, the disorder was cured in 31 cases, while excellent result was seen in 26 cases and obvious improvement in 6 cases. During the procedure, bleeding at puncture site occurred in 16 cases, pulmonary embolism in 2 cases and cerebral hemorrhage in one case. No death occurred. Conclusion Comprehensive nursing measures can effectively prevent or reduce the occurrence of complications, decrease the mortality rate. Therefore, Comprehensive nursing measures are the most helpful nursing care for DVT patients receiving interventional therapy.
ABSTRACT
Objective To discuss the effective nursing measures in interventional therapy for deep vein thrombosis(DVT)of lower extremities in order to improve the successful rate of the procedure and to decrease the occurrence of complications.Methods Comprehensive nursing measures,including general nursing care,specific nursing care and emergency nursing care,were employed in 63 DVT patients receiving interventional therapy.Clinical response and complications were observed.Results After the treatment,the disorder was cured in 31 cases,while excellent result was seen in 26 cases and obvious improvement in 6 cases.During the procedure,bleeding at puncture site occurred in 16 cases,pulmonary embolism in 2 cases and cerebral hemorrhage in one case.No death occurred.Conclusion Comprehensive nursing measures can effectively prevent or reduce the occurrence of complications,decrease the mortality rate.Therefore,Comprehensive nursing measures are the most helpful nursing care for DVT patients receiving interventional therapy.