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.
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.
Tumor immunotherapy includes immune checkpoint inhibitor (ICI), tumor vaccines, and adoptive cell therapy. Immunotherapy, as the main systemic treatment for advanced malignant tumors, kills tumor cells by activating the immune system and prolongs the survival of patients. However, excessive immune responses can cause immune-related adverse events (irAE), causing damage to systemic tissues. ICI are the main tumor immunotherapy drugs that cause optic nerve irAE. The most common optic nerve irAE are optic neuritis, only a few patients appeared arteritic anterior ischemic optic neuropathy. Sudden painless loss of bilateral vision is the most common clinical manifestation. In severe cases, the vision decrease to no light perception. Early diagnosis and early adequate glucocorticoid treatment can improve the symptoms. Therefore, neuro-ophthalmologists and oncologists should know the clinical characteristics of optic nerve irAE, in order to diagnose and treat early and improve the prognosis.
Objective To investigate the prediction of baseline neutrophil-lymphocyte ratio (NLR) on the prognosis of unresectable hepatocellular carcinoma (uHCC) treated with transarterial chemoembolization (TACE) + lenvatinib + camrelizumab. Method The clinical data of 58 patients treated with TACE + lenvatinib + camrelizumab in the Department of Liver Surgery of West China Hospital of Sichuan University from June 2020 to May 2021 were analyzed retrospectively. Results Among the 58 cases included, 7 cases were complete response (CR), 37 cases were partial response (PR), 11 cases were stable disease (SD), and 3 cases were progressive disease (PD). All cases had different degrees of adverse events, including 58 cases of grade 1, 36 cases of grade 2, 35 cases of grade 3, and 1 case of grade 4. The overall response rate (ORR) and disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) were 75.9% (44/58) and 94.8% (55/58), respectively. The hepatectomy rate was 31.0% (18/58) and the conversion success rate was 37.9% (22/58). Multivariate logistic regression analysis showed that NLR was an independent risk factor for ORR (OR=0.093, P=0.008). All cases were followed up for 16–60 weeks, with a median follow-up of 34 weeks. Overall survival situation (χ2=4.163, P=0.041) and progression free survival situation (χ2=10.626, P=0.001) in the low NLR group were better than those of the high NLR group. Conclusion NLR has clinical significance in predicting the prognosis of uHCC cases underwent TACE + lenvatinib + camrelizumab, which is worthy of further study.
Objective To systematically review the sex differences in efficacy of immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) patients. Methods We conducted a computer search of Medline, The Cochrane Library, and EMbase from inception to November 2022 to identify randomized controlled trials (RCTs) assessing the efficacy of ICIs in patients with NSCLC. A meta-analysis was performed using RevMan 5.4 software. ResultsFinally 16 RCTs with a total of 9 653 patients were included, and the modified Jadad scale score was≥4 points. Meta-analysis results showed that in female NSCLC patients receiving immune therapy, the median overall survival (OS) [HR=0.72, 95%CI (0.61, 0.85), P<0.001] was longer than that in males [HR=0.73, 95%CI (0.69, 0.78), P<0.001]. Males [HR=0.64, 95%CI (0.58, 0.71), P<0.001] had an advantage over females [HR=0.76, 95%CI (0.57, 1.03), P=0.760] in median progression-free survival (PFS). Conclusion Females receiving ICIs have an advantage over males in terms of median OS. However, males tend to derive greater benefit from ICIs in terms of median PFS.
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.
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 summarize the clinical characteristics, potential molecular mechanisms, and predictive biomarkers of hyperprogressive disease (HPD) associated with the treatment of hepatocellular carcinoma (HCC) with immune checkpoint inhibitors and to explore its clinical implications. MethodsThe relevant domestic and international literature was reviewed to analyze the definition, mechanisms, and predictive factors of HPD. Particular attention was given to key factors affecting HPD development, including clinical characteristics, tumor microenvironment, genetic mutations, and inflammatory factors. ResultsHPD significantly decreased the survival of HCC patients. Its occurrence might be associated with individual variability, dysregulation of the tumor microenvironment, tumor-related genetic mutations, and elevated level of inflammatory factors. Clinical features such as female, advanced age, elevated Child-Pugh score, portal vein tumor thrombus could identify high-risk populations for HPD. Blood-based biomarkers such as neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and alpha-fetoprotein showed potential value in predicting HPD. ConclusionsSystematic investigation of the molecular mechanisms and predictive biomarkers of HPD are crucial for optimizing immunotherapy strategies and improving patient’s outcomes. Large-scale, multi-center studies are needed to achieve precise prediction and personalized intervention in the future.