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.
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.
ObjectiveTo explore the short-term efficacy and safety of pembrolizumab combined with chemotherapy in the neoadjuvant treatment of non-small cell lung cancer. MethodsThe clinical data of 11 male patients with non-small cell lung cancer who underwent pembrolizumab combined with neoadjuvant chemotherapy in the Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to June 2021 were retrospectively analyzed. The average age of the patients was 52.0-79.0 (62.0±6.9) years. The imaging data and pathological changes before and after neoadjuvant treatment were compared, and adverse reactions during neoadjuvant treatment were recorded. Objective remission rate (ORR) and main pathological remission rate (MPR) and pathological complete remission rate (pCR) were the main observation endpoints. ResultsAfter preoperative neoadjuvant therapy with pembrolizumab combined with platinum or paclitaxel, all patients successfully underwent thoracoscopic radical resection of lung cancer. The ORR was 72.7%, and the MPR was 81.8%. Among them, 45.5% of patients achieved pCR. The main adverse reactions were hypoalbuminemia, decreased appetite and nausea. The mortality rate within 30 days after surgery was 0, and no tumor metastasis was observed. ConclusionPembrolizumab combined with neoadjuvant chemotherapy is safe and feasible to treat non-small cell lung cancer, and the short-term efficacy is beneficial.
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.
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.
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.
ObjectiveTo analyze the CT features of immune checkpoint inhibitor-related pneumonia (CIP) and improve the diagnostic accuracy of CIP. MethodsAmong patients with malignant tumor treated with immune checkpoint inhibitors, those who developed pneumonia and rule out other causes of disease were identified. Chest CT Imaging were reviewed to assess special signs, distribution characteristics, severity of pneumonia and radiographic patterns of CIP. ResultsA total of 28 patients were enrolled, including 26 males and 2 females. CT features include ground-glass opacity, centrilobular nodularity, reticular opacity, consolidation, traction bronchiectasis, honeycomb, etc. The lesions predominant involved peripheral lung zone (17/28), lower lung zone (18/28) and posterior lung zone (18/28), with a diffuse distribution (23/28). In most cases the disease involved both lungs (23/28), and a few involved unilateral or single lobe. The most common affected lobes were the lower lobe of the right lung (25/28) and the lower lobe of the left lung (20/28), followed by the upper lobe of the right lung (18/28). Mean pneumonia severity score was 5.5, standard deviation was 3.8, and range was 1 - 15. The most common radiographic patterns of CIP were nonspecific interstitial pneumonia (11/28) and hypersensitivity pneumonia (10/28). The second was organizing pneumonia (6/28). ConclusionsThe CT manifestations of CIP have certain specificity. Combined with the history of drug treatment and clinical symptoms of patients, the early and correct diagnosis can be obtained.
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.