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 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 recent years, immune checkpoint inhibitors have begun to be used in targeted cancer therapy. Despite the favorable results in terms of oncological outcomes, these treatments have been associated with a variety of immune-related adverse events. Neuromuscular disease is more common among adverse events involving the nervous system. With the increasing use of immune checkpoint inhibitors, the early recognition and treatment of neuromuscular immune-related adverse events are very important. In this review, we are focused on the epidemiology, pathogenesis, clinical manifestations, evaluation, diagnosis, and treatment of neuromuscular diseases (including peripheral neuropathy, myasthenia gravis, and myositis) caused by immune checkpoint inhibitors, aiming to provide a theoretical basis for improving the diagnosis and treatment ability of users of immune checkpoint inhibitors for such neuromuscular diseases and reducing the disability rate and mortality rate caused by immune checkpoint inhibitors.
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.
The treatment of patients with advanced lung cancer has been revolutionized with the advent of immunotherapy. However, not all patients can benefit equally from immunotherapy. In recent years, the relationship between intestinal flora and the efficacy of immunotherapy has gradually attracted scholars' attention. During the treatment of immune checkpoint inhibitors, the use of antibiotics, proton pump inhibitors and other drugs will affect the patient's intestinal flora, thus affecting the efficacy of immune checkpoint inhibitors, leading to poor prognosis of patients. This review will discuss that antibiotics and proton pump inhibitors reduce the efficacy of immunotherapy by affecting the diversity of intestinal flora, in order to facilitate the rational use of related drugs in clinical practice and improve the patient's outcomes.
ObjectiveTo investigate feasibility, safety, and problems to be solved in treatment with programmed death receptor protein-1 (PD-1) monoclonal antibody for patients with recurrent liver cancer after liver transplantation (LT).MethodAll of the domestic and foreign cases reports about the application of PD-1 monoclonal antibody in the patients with recurrent liver cancer after the LT were analyzed and summarized.ResultsIn six patients with recurrent liver cancer after the LT who received the PD-1 monoclonal antibody, the acute graft rejections were observed in 3 patients, 2 patients had the progressive disease but there was no evidence of the graft rejection, 1 patient achieved the complete response and there was no evidence of graft rejection and no side effects.ConclusionsAt present, effect of PD-1 monoclonal antibody therapy is still not sure in patients with recurrent liver cancer after LT. If PD-1 monoclonal antibody is used off-label, close surveillance is needed to discovery possible acute graft rejection.
Objective To systematically review the efficacy and safety of immune checkpoint inhibitors combined with chemotherapy in the treatment of triple-negative breast cancer. Methods The PubMed, Cochrane Library, Embase, Web of Science, CNKI, WanFang Data and VIP databases were searched for randomised controlled trials (RCTs) of immune checkpoint inhibitors combined with chemotherapy versus chemotherapy alone for triple-negative breast cancer from inception to April 1, 2024. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.4 software. Results A total of 13 RCTs involving 5 416 patients were included. The results of meta-analysis showed that the pathologic complete response rate (pCR) (OR=2.09, 95%CI 1.37 to 3.19, P<0.01), progression-free survival (PFS) (HR=0.75, 95%CI 0.67 to 0.83, P<0.01) and overall survival (OS) (HR=0.87, 95%CI 0.79 to 0.96, P<0.01) were significantly better than those in the control group. The results of subgroup analysis showed that there were statistically significant differences in PFS (P<0.01) and OS (P=0.02) between PD-L1-positive and PD-L1-negative patients, but there was no statistically significant difference in pCR between PD-L1-positive patients and PD-L1-negative patients (P=0.36). There was a statistically significant difference in pCR between node-positive patients and node-negative patients (P=0.03). There was no statistically significant difference in pCR between patients treated with PD-1 inhibitors and PD-L1 inhibitors (P=0.32); and there was no significant difference in PFS (P=0.19) or OS (P=0.99) between patients treated with PD-1 inhibitors and PD-L1 inhibitors. Compared with those in the control group, the incidences of serious adverse events (RR=1.36, 95%CI 1.09 to 1.70, P<0.01) and immune-related adverse events (RR=2.98, 95%CI 1.66 to 5.35, P<0.01) were higher in the experimental group, and the common immune-related adverse events were hypothyroidism and hyperthyroidism.Conclusion The existing evidence shows that immune checkpoint inhibitors combined with chemotherapy are more effective than chemotherapy alone in the treatment of triple-negative breast cancer, and the combination therapy has a higher incidence of adverse reactions. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.
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.
Objective Risk factors for real-word immune checkpoint inhibitor-related pneumonitis in patients with lung cancer were analyzed by systematic analysis. Methods Computerized retrieval of PubMed, EMbase, Web of Science, the Cochrane Library , WanFang Data, CNKI and VIP databases was carried out. Studies were collected from the database establishment to March 2023. Three researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Meta-analysis was performed using RevMan5.4.1software. Results A total of 18 studies were included with a total of 4 990 patients. The results of meta-analysis showed that, interstitial pneumonia [odds ratio (OR)=9.32, 95% confidence interval (CI) 4.66 - 18.67, P<0.01], smoking history (OR=2.39, 95%CI 1.29 - 4.45, P<0.01), chronic obstructive pulmonary disease (COPD) (OR=5.54, 95%CI 2.96 - 10.36, P<0.01), chest radiotherapy (OR=2.74, 95%CI 1.80 - 4.19, P<0.01), pulmonary fibrosis (OR=7.46, 95%CI 4.25 - 13.09, P<0.01), high programmed death ligand 1 (PD-L1) expression (OR=2.98, 95%CI 1.71 - 5.22, P<0.01), high absolute eosinophil count (AEC) (OR=3.92, 95%CI 2.17 - 7.08, P<0.01) and pembrolizumab (OR=2.90, 95%CI 1.56 - 5.37, P<0.01) were independent risk factors for immune checkpoint inhibitor-related pneumonitis in lung cancer patients. Conclusions Interstitial pneumonia, smoking history, COPD, Chest radiotherapy, pulmonary fibrosis, high PD-L1expression, high AEC and pembrolizumab are independent risk factors for immune checkpoint inhibitor-related pneumonitis in lung cancer patients. Due to insufficient evidence on the risk factors of low albumin, more studies are needed to further identify it.
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.