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 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.
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 definition, incidence, risk factors, potential pathogenesis, biomarkers, and choice of follow-up treatment strategies of hyperprogressive disease (HPD).MethodDomestic and international literatures were collected to summarize the research progress of HPD in patients with malignant tumors who treated with immune checkpoint inhibitors (ICIs).ResultsThe research types of HPD were scattered, the sample size was limited, the definition standard was different, and there was lack of prospective validation studies. Therefore, the early warning assessment and molecular mechanism of HPD would become the next focus of the study of immunotherapy.ConclusionICIs can greatly improve the survival time of some patients with advanced malignant tumor, although some patients have HPD during treatment, but the incidence is relatively low.
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 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 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 immunotherapy for metastatic breast cancer. Method Literatures about immunotherapy for metastatic breast cancer were reviewed by searching the literatures in domestic and foreign database. Results In recent years, immunotherapy had been initially attempted in patients with metastatic breast cancer and showed its unique value. It provided a new way to improve the therapeutic effect and prolong the survival time of patients with metastatic breast cancer. ConclusionsImmunotherapy is the most effective in triple-negative metastatic breast cancers. The immuno-oncology needs to be developed to improve the clinical benefits of immunotherapy for breast cancer.
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.
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.