Lung cancer is the most frequent cancer and the leading cause of cancer death all around the world. Anti-programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) therapies have significantly improved the outcomes of non-small cell lung cancer (NSCLC) patients in recent years. However, the objective response rate in non-screened patients is only about 20%. It is very important to screen out the potential patients suitable for immunotherapy. Immunohistochemical staining of tumor tissue biopsies with PD-L1 antibodies can predict the therapeutic response to immunotherapy to some extent, but it still has some limitations. Recently some clinical studies have shown that PD-L1 expression in circulating tumor cells (CTC-PD-L1) is a potential independent biomarker and may provide important information for immunotherapy in NSCLC. This article will review technology for CTC-PD-L1 detection and the predictive value of CTC-PD-L1 for immunotherapy in NSCLC and review the latest clinical research progress.
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.
Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) signaling pathway has been found capable of affecting anti-tumor immune effect in many malignancies in recent years. Patients who are diagnosed with advanced non-small cell lung cancer (NSCLC) have considerable responses after receving inhibitors against PD-1/PD-L1. This paper reviews the clinical progress of PD-1/PD-L1 inhibitors in the treatment of NSCLC.
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.
Objective To systematically evaluate the efficacy and safety of a combination regimen of PD-1/PD-L1 immune checkpoint inhibitors in the first-line treatment of advanced non-small cell lung cancer. Methods Randomized controlled trials (RCTs) of PD-1/PD-L1 inhibitor combination regimen in the first-line treatment of advanced non-squamous NSCLC were systematically retrieved from the Chinese and English electronic databases from inception to September 2023. The combination regimen includes PD-1/PD-L1 inhibitor+chemotherapy, PD-1/PD-L1 inhibitor+chemotherapy+anti-angiogenic agents (bevacizumab), and PD-1/PD-L1 inhibitor+CTLA4 inhibitor (ipilimumab). The network meta-analysis was performed using StataMP16.0 and R4.2.0 software. ResultsA total of 13 RCTs were collected, including 7 764 patients. In terms of effectiveness, compared with chemotherapy, several regimens improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Among them, toripalimab (Tor) plus chemotherapy (CT) may be associated with the best OS, and nivolumab plus bevacizumab and chemotherapy (Niv+Bev+CT) may provide the best PFS. Pembrolizumab (Pem) combined with CT was associated with the best treatment regimen for improving ORR. In terms of safety, except sintilimab (Sin) and Pem, the incidence of grade≥3 adverse events of all treatment regimens was significantly higher than that of chemotherapy (P<0.05). The incidence of AEs≥3 grade in Cam+CT was higher than that in Sin+CT (OR=0.44, 95%CI 0.25-0.80) and Pem+CT (OR=0.52, 95%CI 0.31-0.88). And the incidence of ≥3grade AEs in Atezolizumab (Ate) +Bev+CT (OR=2.32, 95%CI 1.14-4.71; OR=1.97, 95%CI 1.02-3.79) was also higher than that in Sin+CT and Pem+CT (P<0.05). Conclusion In non-squamous NSCLC patients, PD-1 inhibitor combined with chemotherapy can bring more benefits to advanced NSCLC patients than chemotherapy alone.
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 screen long non-coding RNAs (lncRNAs) relevant to programmed cell death (PCD) and construct a nomogram model predicting prognosis of hepatocellular carcinoma (HCC). MethodsThe HCC patients selected from The Cancer Genome Atlas (TCGA) were randomly divided into training set and validation set according to 1∶1 sampling. The lncRNAs relevant to PCD were screened by Pearson correlation analysis, and which associated with overall survival in the training set were screened by univariate Cox proportional hazards regression (abbreviation as “Cox regression”), and then multivariate Cox regression was further used to analyze the prognostic risk factors of HCC patients, and the risk score function model was constructed. According to the median risk score of HCC patients in the training set, the HCC patients in each set were assigned into a high-risk and low-risk, and then the Kaplan-Meier method was used to draw the overall survival curve, and the log-rank test was used to compare the survival between the HCC patients with high-risk and low-risk. At the same time, the area under receiver operating characteristic curve (AUC) was used to evaluate the value of the risk score function model in predicting the 1-, 3-, and 5-year overall survival rates of HCC patients in the training set, validation set, and integral set. Then the nomogram was constructed based on the risk score function model and factors validated in clinic, and its predictive ability for the prognosis of HCC patients was evaluated. ResultsA total of 374 patients with HCC were downloaded from the TCGA, of which 342 had complete clinicopathologic data, including 171 in the training set and 171 in the validation set. Finally, 8 lncRNAs genes relevant to prognosis (AC099850.3, LINC00942, AC040970.1, AC022613.1, AC009403.1, AL355974.2, AC015908.3, AC009283.1) were screened out, and the prognostic risk score function model was established as follows: prognostic risk score=exp1×β1+exp2×β2...+expi×βi (expi was the expression level of target lncRNA, βi was the coefficient of multivariate Cox regression analysis of target lncRNA). According to this prognostic risk score function model, the median risk score was 0.89 in the training set. The patients with low-risk and high-risk were 86 and 85, 86 and 85, 172 and 170 in the training set, validation set, and integral set, respectively. The overall survival curves of HCC patients with low-risk drawn by Kaplan-Meier method were better than those of the HCC patients with high-risk in the training set, validation set, and integral set (P<0.001). The AUCs of the prognostic risk score function model for predicting the 1-, 3-, and 5-year overall survival rates in the training set were 0.814, 0.768, and 0.811, respectively, in the validation set were 0.799, 0.684, and 0.748, respectively, and in the integral set were 0.807, 0.732, and 0.784, respectively. The multivariate Cox regression analysis showed that the prognostic risk score function model was a risk factor affecting the overall survival of patients with HCC [<0.89 points as a reference, RR=1.217, 95%CI (1.151, 1.286), P<0.001]. The AUC (95%CI) of the prognostic risk score function model for predicting the overall survival rate of HCC patients was 0.822 (0.796, 0.873). The AUCs of the nomogram constructed by the prognostic risk score function model in combination with clinicopathologic factors to predict the 1-, 3-, and 5-year overall survival rates were 0.843, 0.839, and 0.834. The calibration curves of the nomogram of 1-, 3-, and 5-year overall survival rates in the training set were close to ideal curve, suggesting that the predicted overall survival rate by the nomogram was more consistent with the actual overall survival rate. ConclusionThe prognostic risk score function model constructed by the lncRNAs relevant to PCD in this study may be a potential marker of prognosis of the patients with HCC, and the nomogram constructed by this model is more effective in predicting the prognosis (overall survival) of patients with HCC.
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.
ObjectiveTo understand the molecular mechanism of ferroptosis and its research progress and future prospects in pancreatic cancer. MethodThe relevant literature on the molecular mechanism of ferroptosis and its basic and clinical application in the occurrence and development of pancreatic cancer was retrievaled and reviewed. ResultsFerroptosis was a non-apoptotic form of cell death that depended on iron aggregation, and its molecular biological features included iron ion overload, reactive oxygen species accumulation, lipid peroxidation, and so on. Ferroptosis was closely related to cell metabolism, and the imbalance of ferroptosis caused by abnormal metabolism also existed during the tumorigenesis and progression of pancreatic cancer, which in turn triggered the abnormal proliferation of pancreatic cancer cells and leaded to their progression. By regulating the key molecular signaling pathways of ferroptosis, it was expected to find new drug targets and therapeutic pathways for pancreatic cancer treatment. The results of ferroptosis-related studies so far had shown the potential for future translational research in the field of pancreatic cancer treatment. ConclusionsThe mechanism of ferroptosis is of great value in pancreatic cancer research. At present, there are still many uncharted areas in the study of ferroptosis, and the molecular mechanisms involved are still poorly understood. In the future, as the study of ferroptosis continues, it is expected to provide new ideas for pancreatic cancer treatment and discover new targets for drug development.
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.