Surgery remains as the primary definitive therapy for resectable non-small cell lung cancer (NSCLC) currently. However, quite a few NSCLC patients, especially in the later stage, suffered tumor recurrence after resection. Safer and more effective perioperative treatment is urgently needed to reduce the recurrence risk after NSCLC surgery. Immune checkpoint inhibitors can effectively prevent tumor immune evasion and have been shown to be a feasible, safe and effective neoadjuvant therapy for resectable NSCLC. Nevertheless, certain crucial problems, including the final effect on NSCLC recurrence, the selection of beneficial group and optimal treatment protocol are yet unsolved. Fortunately, several phase Ⅲ randomized controlled trials are ongoing to answer these questions and will hopefully provide stronger evidence.
Objective To summarize the research status and prospect of immunotherapy for biliary tract cancer (BTC). Method The literatures about immunotherapy of BTC at home and abroad in recent years were reviewed. Results Surgical resection was still the first choice and only radical treatment for BTC. However, the recurrence rate of BTC was high, and most of the patients were in the middle and late stage with metastasis and lose the opportunity of operation. Patients with local progression, metastasis or recurrence could only receive chemotherapy and other comprehensive treatment, but they could not get satisfactory results. The continuous update of targeted drugs brings new hope for drug therapy of BTC, and immunotherapy had become a new treatment of tumor targeted therapy following radiotherapy and chemotherapy. ConclusionImmunotherapy can be used as an option for the treatment of advanced BTC and its postoperative recurrence and metastasis, and has attracted more and more attention.
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.
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.
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 recognize the latest research progress of immunotherapy for advanced gastric cancer (AGC). MethodThe domestic and international literature on immunotherapy for AGC in recent years were retrieved and reviewed. ResultsThe immunotherapy for AGC mainly focused on immune checkpoint inhibitors (ICIs), cellular immunity, and antitumor vaccines. The most immunotherapy researched was ICIs, especially for programmed death protein-1 / programmed death protein ligand 1, cytotoxic T lymphocyte associated antigen 4, and lymphocyte activating gene 3. The cellular immunotherapy and tumor vaccine therapy were less relatively. Although immunotherapy alone did not have a particularly good effect, its therapeutic effect was not inferior to that of chemotherapy alone and the incidence of adverse reactions was lower. Moreover, most studies had concluded that the use of immunotherapy in combination with other therapy had shown a good clinical efficacy, especially in combination with anti-human epidermal growth factor receptor 2 antibody, and chimeric antigen receptor T cells targeting Claudin 18.2 site had promising results in the AGC. ConclusionsWith the development of immunotherapy research, the strategies of immunotherapy for AGC are also constantly improving. Precision medicine is important in the process of immunotherapy. Targeted screening suitable patients and adopting precise treatment can further benefit the survival of patients with AGC.
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.
Pancreatic cancer (PC) is a highly malignant tumor of the digestive system and has a concealed onset with rapid progression. The majority of PC patients are diagnosed in the middle to late stages, and the effectiveness of traditional treatment methods for advanced pancreatic cancer is limited, which results in a poor prognosis. Immunotherapy, as a novel treatment strategy, aims to suppress tumor growth and metastasis by modulating and enhancing the human immune system. It has become a hot point in current cancer prevention and treatment. This article will elaborate on the newest advancements in immunotherapy for PC. Furthermore, we point out the major challenges of PC immunotherapy.
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.