ObjectiveTo summarize the mechanism of action of programmed cell death protein 1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors, the application in breast cancer in recent years and the advances in the study of their bio-markers of effects. MethodRelevant literatures on PD-1/PD-L1 inhibitors and the study in the field of breast cancer were reviewed and summarized.ResultsIn recent years, the monotherapy of immune checkpoint inhibitors represented by PD-1/PD-L1 inhibitors or in combination with other therapies had brought new hope for patients with breast cancer especially triple-negative breast cancer (TNBC). However, only a small number of patients could benefit from breast cancer immunotherapy. The current researchers think that the efficacy of these drugs is related to PD-L1 expression in tumor tissue, tumor mutation burden (TMB), high level of microsatellite instability (MSI-H) and deficient mismatch repair (dMMR).ConclusionBreast cancer can benefit from the immunotherapy of PD-1/PD-L1 inhibitors, but formulating personalized medicine model, finding biomarkers that can predict efficacy and selecting patients with breast cancer who can benefit from it for targeted therapy are the new requirements in the new era of breast cancer immunotherapy.
Objective To examine the association between programmed cell death ligand 1 (PD-L1) expression and venous thromboembolism (VTE) risk in lung cancer patients treated with immune checkpoint inhibitors (ICIs). Methods We enrolled adults with lung cancer who initiated ICIs between January 2018 and March 2022 at West China Hospital of Sichuan University. The included patients were divided into PD-L1 TPS<50% group and PD-L1 TPS≥50% group. Clinical outcomes including VTE, pulmonary embolism (PE), and deep venous thrombosis (DVT) were evaluated with cox regression models. Results Of the 519 lung cancer patients receiving ICIs finnaly analyzed (347 cases with PD-L1 TPS<50%; 172 cases with PD-L1 TPS≥50%), VTE developed in 48 cases (9.2%) during the 12-month follow-up, of which 41 cases (7.9%) had DVT, 4 cases (0.8%) had PE, and 3 cases (0.6%) had DVT and PE. A higher incidence of VTE was observed in TPS<50% group versus TPS≥50% group (P=0.026), whereas there was a trend toward an increased rate of DVT, which was not statistically significant (P=0.052). Significant differences in PE were not found (P=0.152). After multivariable adjustment, PD-L1 TPS<50%, ECOG PS≥2, chronic obstructive pulmonary disease, and VTE history were associated with an increased VTE risk (P<0.05). Conclusion VTE occurred in 9.2% of ICI-treated lung cancer patients. PD-L1 TPS<50% was associated with an increased risk of VTE, which should be identified, prevented and intervened early in clinical practice.
ObjectiveTo systematically evaluate the expression of programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in esophageal squamous cell carcinoma and its relationship with prognosis.MethodsThe literature from PubMed, EMbase, The Cochrane Library, Web of Science, CNKI and Wanfang data from inception to February 22, 2020 was searched by computer. Data were extracted and the quality of literature was evaluated using RevMan 5.3 software for meta-analysis. Egger's and Begg's tests were used to evaluate publication bias, and Stata 15.1 software was used for sensitivity analysis.Results A total of 16 articles were included, and there were 3 378 patients with esophageal squamous cell carcinoma. The methodological index for nonrandomized studies (MINORS) scores were all 12 points and above. The meta-analysis results showed that the positive expression rates of PD-1 and PD-L1 in tumor cells were 37.8% (190/504) and 41.7% (1 407/3 378), respectively. The positive expression of PD-L1 in tumor immune infiltrating cells was 41.7% (412/987). The overall survival (OS) of the tumor cell with high PD-L1 expression was lower than that with low PD-LI expression (HR=1.30, 95%CI 1.01-1.69, P=0.04). The OS of the tumor immune infiltrating cell with high PD-L1 expression was significantly higher than that with low PD-LI expression (HR=0.65, 95%CI 0.53-0.80, P<0.0001).ConclusionPD-L1 has a high expression rate in esophageal squamous cell carcinoma and is an important factor for the prognosis of esophageal squamous cell carcinoma.
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.
We reported three cases of stageⅢ/N2 non-small cell lung cancer (NSCLC) treated with neoadjuvant immunotherapy and stereotactic body radiation therapy (SBRT) in our hospital, including 2 males and 1 female with a mean age of 65.7 years. The patients received two doses of the programmed cell death protein-1 inhibitor toripalimab after 1 week of SBRT. Thereafter, surgery was planned 4-6 weeks after the second dose. One patient achieved pathologic complete response, one achieved major pathologic response (MPR), and one did not achieve MPR with 20% residual tumor. There were few side effects of toripalimab combined with SBRT as a neoadjuvant treatment, and the treatment did not cause a delay of surgery.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Although surgery can cure some early-stage resectable patients, the postoperative recurrence rate remains as high as 30%-55%. Perioperative immune checkpoint inhibitor (ICI) therapy, which includes "neoadjuvant" therapy before surgery and "adjuvant" therapy after surgery, has significantly improved survival outcomes in resectable NSCLC patients. Large clinical studies, such as CheckMate 816, have demonstrated the superiority of neoadjuvant ICIs combined with chemotherapy in increasing the pathological complete response rate (pCR) and prolonging event-free survival (EFS). However, even with these advanced treatments, some patients do not achieve long-term benefits and experience early recurrence. This paper reviews the latest research progress of perioperative ICIs in NSCLC treatment, particularly the effectiveness of neoadjuvant chemoimmunotherapy in improving pCR and extending EFS. It further explores the recurrence patterns, resistance mechanisms, and potential biomarkers in NSCLC patients after neoadjuvant immunotherapy. By integrating basic research and clinical data, we analyze the mechanisms of early recurrence following perioperative immunotherapy and discuss future research directions and therapeutic strategies, providing new insights into precision treatment and recurrence prevention for NSCLC patients.
Objective To summarize the research progress of microRNA in acute pancreatitis. Methods By reading the domestic and international literatures published in recent years, to summarize the research progress of microRNA in acute pancreatitis. Results In recent years, researches had found that microRNA could be used as a biomarker for acute pancreatitis to predict and determine the occurrence, development, and complications of acute pancreatitis. MicroRNA could regulate the programmed cell death of acute pancreatitis, and played an important role in the development of inflammation and complications, it also could be used as a therapeutic target for acute pancreatitis. Conclusions MicroRNA plays an important role in the development of acute pancreatitis. Researching the mechanism of microRNA in acute pancreatitis is helpful for the treatment and prevention of acute pancreatitis.
Objective To investigate the necessity of further surgery for patients with locally advanced esophageal squamous cell carcinoma following treatment with the programmed cell death-1 (PD-1) inhibitor combined with chemotherapy, and to assess its impact on survival. MethodsPatients with stage ⅡA to ⅢB esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at our hospital from January 2020 to June 2022 were selected for this study. Based on whether they underwent surgery after receiving PD-1 inhibitor combined with chemotherapy, patients were divided into a surgery group and a non-surgery group. We compared the general clinical data, side effects, clinical complete response rates, progression-free survival (PFS), and overall survival (OS) between the two groups. Results A total of 58 patients were included in the study, comprising 45 males and 13 females, with an average age of (65.5±6.9) years. There were no statistical differences in general clinical data or adverse reactions between the two groups. Univariate analysis revealed that the objective response rate and surgery were significantly associated with PFS (P<0.05). Binary logistic regression analysis showed that surgery was the only independent risk factor for PFS (P=0.003). Kaplan-Meier survival analysis showed that the PFS and OS in the surgery group were significantly higher than those in the non-surgery group (HR=0.13, 95%CI 0.036 to 0.520, P＜0.001; HR=0.17, 95%CI 0.045 to 0.680, P=0.004). ConclusionAfter treatment with the PD-1 inhibitor combined with chemotherapy, patients with locally advanced esophageal squamous cell carcinoma still require surgical intervention to achieve improved PFS and OS.
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.
Objective To analyze the predictive value of serum copeptin, pentraxin 3 (PTX3), and soluble programmed cell death ligand 1 (sPD-L1) for poor prognosis in children with neonatal purulent meningitis. Methods Children with neonatal purulent meningitis admitted to the Department of Pediatrics, the Second Hospital of Handan between September 2020 and February 2023 were selected. According to the Gesell developmental scale score, the children were separated into a good prognosis group and a poor prognosis group. The correlation between serum levels of copeptin, PTX3, sPD-L1 and the prognosis of neonatal purulent meningitis were analyzed using Spearman correlation coefficient. The correlation of serum levels of copeptin, PTX3, and sPD-L1 with white blood cell count (WBC) and procalcitonin (PCT) were analyzed using Pearson correlation analysis. The area under the curve (AUC) of serum copeptin, PTX3, and sPD-L1 in predicting the prognosis of neonatal purulent meningitis were obtained by plotting the receiver operator characteristic curve. The factors affecting the prognosis of neonatal purulent meningitis were analyzed using multiple logistic regression analysis. Results A total of 107 children were included. Among them, 79 cases had good prognosis and 28 cases had poor prognosis. The serum levels of copeptin, PTX3, sPD-L1, WBC and PCT in the poor prognosis group were obviously higher than those in the good prognosis group (P<0.05). The levels of serum copeptin, PTX3, and sPD-L1 were positively correlated with the prognosis, WBC, and PCT of neonatal purulent meningitis (P<0.05). The results of logistic regression analysis showed that copeptin, PTX3, and sPD-L1 were risk factors affecting the prognosis of neonatal purulent meningitis (P<0.05). The AUC for predicting the prognosis of neonatal purulent meningitis with the combination of serum copeptin, PTX3, and sPD-L1 was 0.976, and the combined predictive value of the three was better than predicting separately (P<0.05). Conclusions Copeptin, PTX3, and sPD-L1 are abnormally upregulated in the serum of children with poor prognosis of neonatal purulent meningitis. The combination of the three can improve the predictive value for poor prognosis of neonatal purulent meningitis.