Objective To summarize the research progress of programmed cell death protein 1 (PD-1)/programmed cell death protein-ligand 1 (PD-L1) inhibitors before liver transplantation of liver cancer. Method The literatures on the application of PD-1/PD-L1 inhibitors before liver transplantation of liver cancer were collected and reviewed. Results PD-1/PD-L1 inhibitors preoperatively treated liver transplantation recipients had a low incidence of postoperative rejection, and routine usage of hormone and immune tolerance induction therapy in liver transplantation recipients might reduce the incidence of rejection caused by PD-1/PD-L1 inhibitors. Conclusion Preoperative usage of PD-1/PD-L1 inhibitors have more benefits than risks for patients with advanced liver cancer.
Most immune-related adverse event (irAE) associated with immune checkpoint inhibitors (ICIs) resulted from excessive immune response against normal organs. The severity, timing, and organs affected by these events were often unpredictable. Adverse reactions could cause treatment delays or interruptions, in rare cases, pose a life-threatening risk. The mechanisms underlying irAE involved immune cell dysregulation, imbalances in inflammatory factor expression, alterations in autoantibodies and complement activation, even dysbiosis of intestinal microorganisms. However, the mechanisms of irAE occurrence might differ slightly among organs due to variations in their structures and the functions of resident immune cells. Future research should focus on the development of targeted drugs for the prevention or treatment of irAE based on the mechanisms by which irAE occurs in different organs. A deeper understanding of the mechanisms underlying irAE occurrence would aid clinicians in effectively utilizing ICIs and provide valuable guidance for their clinical application.
Brain metastases are the most common intracranial malignant tumors in adults. Radiotherapy isa common treatment for brain metastases. In particular, stereotactic radiosurgery can control tumors well, and can significantly reduce the impact on cognitive function compared with whole brain radiation therapy. Immune checkpoint inhibitors have less toxic side effects in the treatment of patients with advanced tumors, and show good survival advantages. This article introduces radiotherapy, immunotherapy, stereotactic radiosurgery combined with immune checkpoint inhibitors for brain metastases, discusses the mechanism of stereotactic radiosurgery combined with immune checkpoint inhibitors, and its therapeutic value and research progress in brain metastases, aiming to provide a theoretical basis for the better application of stereotactic radiosurgery combined with immune checkpoint inhibitors to brain metastases.
Objective To analyze the clinical features of immune checkpoint inhibitor-related pneumonia (CIP) in patients with lung cancer. Methods The case data of patients with CIP admitted to Zhongshan Hospital of Fudan University from January 2017 to December 2020 were retrospectively collected, and the basic data, clinical manifestations, imaging data, laboratory examination results, treatment and prognosis of the patients were analyzed. Results The ratio of male to female was 18:1, and the median age was 65 years (from 41 to 74 years). Fourteen patients received a programmed death protein-1 (PD-1) inhibitor and five patients received a programmed death protein-ligand-1 (PD-L1) inhibitor. The median time to CIP was 3.5 months. The respiratory symptoms of 15 patients were dyspnea in 11 cases, cough in 9 cases, chest tightness in 8 cases, fever in 4 cases, expectoration in 4 cases and hemoptysis in 2 cases. Chest CT findings mainly showed interstitial pneumonia, including 8 cases of implicit organizational pneumonia (COP), 7 cases of non-specific interstitial pneumonia (NSIP), 2 cases of acute interstitial pneumonia, and 2 cases of allergic pneumonia. C-reactive protein, erythrocyte sedimentation rate and lactate dehydrogenase were higher in CIP than before, and the difference was statistically significant. Follow-up observation was performed in 3 patients alone, 14 patients were treated with glucocorticoid alone, 2 patients were treated with immunosuppressant therapy, 19 patients had stable or more absorption of pneumonia lesions, and 5 patients had restarted immunotherapy. There were no deaths from CIP. Conclusions CIP mainly occurs in men, with slow onset, lack of specificity in clinical manifestations, and increased inflammatory indicators. Imaging findings are mainly NSIP and COP changes. Early identification, diagnosis and rational application of glucocorticoid therapy have good effects.
Lung cancer is the leading cause of cancer-related deaths worldwide. Although improvement has been achieved in platinum-based chemotherapy and tyrosine kinase inhibitors-based molecular targeted therapy, they still have limitations. Immunotherapy has recently emerged as a very effective new treatment, and there is now growing enthusiasm in cancer immunotherapy worldwide. We summarized the effects of immune checkpoint inhibitors in clinical trials, and the current status and progress of anti programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) agents in lung cancer treatment. Attention has been paid to finding out the factors which influence the therapeutic effect of anti-PD-1/PD-L1 therapy and reducing the occurrence of adverse events.
In recent years, the incidence of primary liver cancer has been increasing, among which hepatocellular carcinoma (HCC) being the most common subtype. The treatment of early HCC is mainly surgery, but most patients are not diagnosed until the late stage of the disease. The treatment methods and effects are very limited and the prognosis is very poor. Although targeted therapy has prolonged the overall survival of patients with HCC, the overall efficacy is unsatisfactory. The emergence of immunotherapy has brought new therapeutic prospects for HCC. Immune checkpoint inhibitors, among which programmed death-1/programmed death ligand-1 and cytotoxic T-lymphocyte associated antigen-4 are the representative immunological checkpoints, have attracted more attention. This article will introduce the application of immune checkpoint inhibitors in the treatment of advanced HCC, in order to provide a theoretical basis for the use of immune checkpoint inhibitors in the treatment of advanced HCC.
ObjectiveTo investigate the efficacy, safety, and problems of immune checkpoint inhibitors (ICIs) and their combination with other therapies in treatment of patients with advanced hepatocellular carcinoma (HCC).MethodThe relevant literatures on the clinical trials of ICIs and their combination therapy in patients with advanced HCC in recent years were collected and reviewed.ResultsThe therapeutic effects of programmed death receptor 1 and its ligands and cytotoxic T lymphocyte associated antigen 4 monoclonal antibodies in clinical trials of patients with advanced HCC were better, but the therapeutic effect of single drug was limited. Double immunotherapy and its combination with anti-angiogenesis inhibitors, molecular targeted drugs, and local therapy might make patients achieve more remarkable therapeutic effects, especially in combination with anti-angiogenesis inhibitors.ConclusionICIs could remarkably improve survival prognosis of patients with advanced HCC, combined immunotherapy has better survival benefits.
ObjectiveTo review the present situation of immune checkpoint inhibitors in treatment of advanced hepatocellular carcinoma (HCC), and discuss the advance of combined immunotherapy.MethodsThe relevant literatures on researches of immune checkpoint inhibitors in the treatment of advanced HCC were retrieved to make an review.ResultsImmunotherapy intervention had been becoming a novel and promising therapeutic approach for HCC, which could suppress the progression of aggressive tumor and could inhibit tumor recurrence and metastasis shown in some pre-clinical trials. Other studies had found that the combined strategy of specific immunotherapy and conventional therapies could significantly improve the clinical outcomes of HCC patients.ConclusionCombined immunotherapy can significantly improve the clinical outcomes of HCC and benefit more patients with advanced HCC.
In December 2019, an outbreak of pneumonia associated with the coronavirus disease 2019 (COVID-19) occurred in Wuhan, China. The lung imaging finding is like that of the lung cancer immune checkpoint inhibitors (ICI) associated pneumonia. Therefore, we speculated that they may have similar pathogenesis and treatment strategies, which is reviewed in this article in order to provide some reference to timely and effectively reduce the fatality rate of COVID-19.
ObjectiveTo analyze the efficacy and safety of immunotherapy and bevacizumab combined with chemotherapy (BIC), bevacizumab combined with chemotherapy (BC), chemotherapy (CT), immunotherapy combined with chemotherapy (IC), bevacizumab combined with immunotherapy (BI), bevacizumab (B) in the first-line treatment of advanced wild-type non-squamous non-small cell lung cancer. MethodsThe PubMed, Embase, Cochrane Library and Web of Science databases were searched to collect phase Ⅱ/Ⅲ randomized controlled trials (RCTs) related to the objectives of the study from January 2010 to December 1, 2022. After two investigators independently screened the literatures, extracted the data and evaluated the risk of bias of the included studies, a reticular meta-analysis was performed using R 3.6.1 software. ResultsA total of 11 RCTs were finally included, including 5 329 patients and six treatment combinations. Meta-analysis results showed that BIC was superior to CT for progression-free survival (PFS) (HR=0.34, 95% CI 0.18 to 0.69), but BIC did not show a significant advantage over the other groups for overall survival (OS). Bayesian ranking results showed that the BIC group had the greatest probability in terms of OS, PFS, and ORR. Among all programmed death ligand 1 (PD-L1) expressing subgroups, there was no significant difference in OS between BIC, BC, IC, CT, BI, and B. Compared with CT, IC was significantly improved in OS (HR=0.68, 95%CI 0.52 to 0.92), PFS (HR=0.58, 95%CI 0.45 to 0.75), and ORR (HR=0.47, 95%CI 0.33 to 0.66). ConclusionIn the first-line treatment of wild-type advanced non-squamous NSCLC, immunotherapy and bevacizumab combined with chemotherapy may improve the efficacy in the short term, but do not change the long-term survival time. Immunotherapy combined with chemotherapy can significantly improve the survival time and prognosis of patients compared with chemotherapy alone. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.