Development in immunotherapy of lung cancer / 中国胸心血管外科临床杂志

@#Lung cancer is the leading cause of cancer-related deaths worldwide. Although improvement has been achieved in platinum-based chemotherapy and tyrosine kinase inhibitors-based molecular targeted therapy, they still have limitations. Immunotherapy has recently emerged as a very effective new treatment, and there is now growing enthusiasm in cancer immunotherapy worldwide. We summarized the effects of immune checkpoint inhibitors in clinical trials, and the current status and progress of anti programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) agents in lung cancer treatment. Attention has been paid to finding out the factors which influence the therapeutic effect of anti-PD-1/PD-L1 therapy and reducing the occurrence of adverse events.

A prediction model of pathological complete response in patients with locally advanced rectal cancer after PD-1 antibody combined with total neoadjuvant chemoradiotherapy based on MRI radiomics / 中华胃肠外科杂志

Objective: To construct a prediction model of pathologic complete response (pCR) in locally advanced rectal cancer patients who received programmed cell death protein-1 (PD-1) antibody and total neoadjuvant chemoradiotherapy by using radiomics based on MR imaging data and to investigate its predictive value. Methods: A clinical diagnostic test study was carried out. Clinicopathalogical and radiological data of 38 patients with middle-low rectal cancer who received PD-1 antibody combined with total neoadjuvant chemoradiotherapy and underwent TME surgery from January 2019 to September 2021 in our hospital were retrospectively collected. Among 38 patients, 23 were males and 15 were females with a median age of 68 (47-79) years and 13 (34.2%) a chieved pCR. These 38 patients were stratified and randomly divided into the training group (n=26) and test group (n=12) for modeling. All the patients underwent rectal MRI before treatment. The clinical, imaging and radiomics features of all the patients were collected, and the clinical feature model and radiomics model were constructed. The receiver operating characteristic (ROC) curves of each model were drawn, and the constructed model was evaluated through the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Results: There were no significant differences in age, gender, primary location of tumor and postoperative pathology between the two groups (all P>0.05). Forty-one features were extracted from region of interest in each modality, including 9 first-order features, 24 gray level co-occurrence matrix features and 8 shape features. From 38 patients, 41 features were extracted from each imaging modality of baseline and preoperative DWI and T2WI images, totally 164 features. Only 4 features were preserved after correlation analysis between each pair of features and t-test between pCR and non-pCR subjects. After LASSO cross validation, only the first-order skewness of the baseline DWI image before treatment and the volume in the baseline T2WI image before treatment were retained. The area under the curve, sensitivity, specificity, positive and negative predictive values of the prediction model established by applying these two features in the training group and the test group were 0.856 and 0.844, 77.8% and 100.0%, 88.2% and 75.0%, 77.8% and 66.7%, 88.2% and 100.0%, respectively. The decision curve analysis of the radiomics model showed that the strategy of this model in predicting pCR was better than that in treating all the patients as pCR and that in treating all the patients as non-pCR. Conclusion: The pCR prediction model for rectal cancer patients receiving PD-1 antibody combined with total neoadjuvant radiochemotherapy based on MRI radiomics has the potential to be used in clinical screening or rectal cancer patients who can be spared from radical surgery.

Current status, controversy and challenge in the neoadjuvant immunotherapy of colorectal cancer / 中华胃肠外科杂志

Neoadjuvant therapy for colorectal cancer is widely used in rectal cancer, locally advanced colon cancer, and resectable metastatic and recurrent colorectal cancer. Mismatch repair deficient(dMMR) and microsatellite instablity-high (MSI-H) colorectal cancer patients who benefit from the efficacy of immune checkpoint inhibitors are expected to further improve the efficacy of traditional neoadjuvant therapy based on radiotherapy and chemotherapy. In this paper, the current status of immunotherapy (with emphasis on immune checkpoint inhibitors) is elucidated, and the opportunities of its application in neoadjuvant therapy are analyzed, including poor sensitivity of dMMR tumors to traditional therapy, good immune response of early tumors, predictable, manageable and controllable toxicity of immune checkpoint inhibitors. Colorectal cancer patients have growing and diverse needs to be met. Current controversies and challenges are analyzed, and the future directions are pointed out, including active screening of benefit groups, exploration of efficacy prediction markers, optimization of neoadjuvant immunotherapy models, attention to efficacy evaluation and new therapeutic endpoints. Neoadjuvant therapy should be effective, moderate and accurate based on the treatment target. It is the prerequisite and basis to guarantee medical safety and improve therapeutic effect to attach importance to the standardization and safety of clinical research and to pay attention to patients' interests and legal and ethical demands.

Effect of antibiotics on treatment efficacy of immune checkpoint inhibitors in nonsmall cell lung cancer: A Meta-analysis / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effects of antibiotics on the treatment efficacy of immune checkpoint inhibitors in NSCLC (non-small cell lung cancer) with Meta-analysis. Methods: Literatures regarding the effects of antibiotics on the treatment efficacy of immune checkpoint inhibitors in NSCLC were searched in Pubmed, Cochrane Library, Embase, EBSCO, Chinese Biomedical Literature Database(CBM) and Chinese Journal Full-text Database(CNKI). RevMan 5.3 software was used in this Meta-analysis. Results: Fourteen articles involving 2 505 NSCLC patients were included in this study. Meta-analysis showed that the application of antibiotics could significantly shorten the PFS (HR=1.14, 95%CI =1.04-1.26, P=0.005) and OS (HR=1.30, 95%CI =1.14-1.47, P<0.0001) of NSCLC patients treated with immune checkpoint inhibitors. Conclusion: Application of antibiotics before, concurrently or after immune checkpoint inhibitors in the treatment of NSCLC may significantly shorten PFS and OS, resulting in adverse effect on treatment efficacy.

Comparison in treatment efficacy and safety between PD-1/PD-L1 inhibitor combined with chemotherapy and chemotherapy alone as first-line treatment for advanced NSCLC:AMeta-analysis / 中国肿瘤生物治疗杂志

@# Objective: To systematically evaluate the efficacy and safety of PD-1/PD-L1 inhibitor combined with chemotherapy as comparing with chemotherapy alone for the first-line treatment of advanced NSCLC (non-small lung cancer). Methods: RCTs (randomized controlled trials) on PD-1/PD-L1 inhibitor combined with chemotherapy compared with chemotherapy alone for the first-line treatment of advanced NSCLC were searched in the PubMed, Cochrane Library, EMbase, EBSCO, Chinese Biomedical Literature Database (CBM), Chinese Journal Full-text Database (CNKI), and Chinese Scientific Journal Full-text Database (VIP). RevMan 5.2 software was used for the Meta-analysis. Results: Six RCTs with 3 238 advanced NSCLC patients were included in this study. Meta-analysis showed that the combination therapy group was more effective than the chemotherapy alone group in OS (HR=0.86, 95%CI=0.79~ 0.94, P=0.0006) and PFS (HR=0.81, 95%CI=0.78~0.84, P<0.00001). The incidence of adverse reactions, such as thrombocytopenia of grade 1-5, vomiting, diarrhea, hypothyroidism, hyperthyroidism, rash, pneumonitis, colitis, hepatitis, dysgeusia, hepatitis of grade 3-5 and colitis, in combined treatment group were all higher than those in chemotherapy alone group, the differences were statistically significant (P<0.01 or P<0.05). Conclusions: Compared with chemotherapy alone, PD-1/PD-L1 inhibitor combined with chemotherapy can significantly improve the OS and PFS of patients with advanced NSCLC in the first-line treatment, while the overall incidence of adverse reactions is higher than chemotherapy.

Research progress of PD-1/PD-L1 in head and neck squamous cell carcinoma / 中国肿瘤临床

Head and neck squamous cell carcinoma (HNSCC) is a kind of malignant tumor characterized by metastasis and local invasion. Its recurrence rate is high after surgery and radiotherapy, and the prognosis and quality of life are poor. In recent years, programmed death-1 (PD-1) inhibitors have been recommended in National Comprehensive Cancer Network (NCCN) guidelines for the treatment of recurrent, unresectable, and metastatic HNSCC, and their efficacy has been remarkable. PD-1 inhibitors constitute a new treatment for the patients with advanced HNSCC who are refractory to platinum-based chemotherapy and can increase the probability of surgical resection, reduce the risk of postoperative dysfunction, and improve the survival and quality of life. This article reviews the structure and mechanism of the PD-1/PD-L1 immunocheckpoint, as well as research progress on its inhibitors in the treatment of HNSCC.

Progress on Anticancer Effects of PD-1/PD-L1 Checkpoint Inhibitors / 中国药学杂志

This artical explained the biological action mechanism of PD-1/PD-L1 monoclonal antibodies through reactivating the immune response of T cells to tumor cells immune response, analyzed the detection reports on the targets, introduced the clinical manifestations and indications research results, and looked into their development potential in the field of anticancer therapy. It's important to rationally use PD-1/PD-L1 monoclonal antibodies to decrease immune-mediated adverse events as well as maximizing the therapeutic effect. Furthermore, we should not only see the accomplishment in anticancer therapy, but also gain insight into its development direction in the field of anticancer research based on the therapeutic idea of inducing autoimmune system to kill tumor cells.

Establishment of a lung cancer mouse model with humanized immunity and its role in efficacy evaluation of programmed death-1 inhibitors / 上海交通大学学报（医学版）

Objective:To establish a lung cancer mouse model with humanized peripheral blood mononuclear cells (PBMC) expressing programmed death-ligand 1 (PD-L1), and study the role of the model in evaluating the efficacy of programmed death-1 (PD-1) inhibitors. Methods:Fresh biopsy tissue samples or tumor cells in malignant pleural effusion from the patients with advanced non-small cell lung cancer were inoculated subcutaneously in CB17-SCID mice to establish patient-derived xenograft (PDX) models. The expression of PD-L1 in PDX models was detected by immunohistochemistry. The mature human PBMC and PDX model tumor cells were mixed and then inoculated into NCG mice to establish a PDX model of lung cancer with humanized immunity, on which the efficacy of PD-1 inhibitor was verified. Results:Among the PDX models established by 16 clinical samples, 2 were strongly positive for PD-L1, 4 were positive, and the rest were negative. In the PDX model with strongly positive PD-L1, the tumor growth inhibition rate of cindilimab, an inhibitor of PD-1, was 82.6%, 21 days after the initial administration; in the PDX model with negative PD-L1, the inhibitor of PD-1 showed no antitumor activity. Conclusion:A PD-L1-expressing lung cancer mouse model with humanized immunity is successfully established and the efficacy of PD-1 inhibitor can be evaluated on the model.

Research progress of PD-1/PD-L1 in small cell lung cancer / 中国肿瘤临床

Small-cell lung cancer (SCLC) has a high degree of malignancy and is characterized by strong invasiveness, rapid growth, and early metastasis. SCLC is sensitive to initial treatment with chemotherapy and radiotherapy, but it can easily relapse and has a poor prognosis. Both programmed death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) antagonists activate the immune response of tumor cells by activating T cells, and have shown exciting curative effects in clinical studies of SCLC, thereby becoming powerful po-tential agents to treat SCLC in the future. This article aims to illustrate the progress of PD-1/PD-L1 inhibitors in the treatment of SCLC, as well as the role of PD-L1 expression and tumor mutation burden (TMB) as a biomarker in SCLC.

The expression and significance of PD-1 and PD-L1 in peripheral blood mononuclear cells of OLP patients / 实用口腔医学杂志

Objective:To explore the expression of PD-1 mRNA and PD-L1 mRNA in peripheral blood mononuclear cells(PBMCs)of OLP patients.Methods:The peripheral blood lymphocyte subsets (CD3 +,CD4 +,CD8 +,CD1 9 +,CD1 6 ++56 +)and humoral immunity indexes (lgG,lgA,lgM,C3,C4)were detected in 36 patients with OLP by flow cytometry and nephelometry respectively.The expres-sions of PD-1 mRNA and PD-L1 mRNA in PBMCs of 36 patients with OLP and 1 8 healthy individuals(the controls)were detected by fluorescence quantitative PCR,the correlation of PD-1 mRNA or PD-L1 mRNA with the immune function of OLP patients was analysed. Results:In OLP patients the percentages of peripheral blood lymphocyte subsets (CD3 +,CD4 +,CD8 +,CD1 9 +,CD1 6 + +56 +)as well as the complement of C3 and C4 were lower(P <0.05),the percentages of CD1 9 +(B)and the level of lgMwere higher(P <0.05),the expression levels of PD-1 mRNA and PD-L1 mRNA in rPBMCs were higher(P <0.05)than in the controls.There was positive correla-tion between PD-1 mRNA and PD-L1 mRNA expression level.The expression level of PD-1 mRNA was negatively correlated with CD4 +,but positively with lgG,the expression level of PD-L1 mRNA was positively correlated with CD1 9 +.Conclusion:The up-regu-lation of PD-1 mRNA and PD-L1 mRNA in PBMCs is correlated with the immunity of OLP patients.PD-1 /PD-L1 pathway may play an important role in immune pathogenesis of OLP.

Prognostic Implication of Programmed Death-1-Positive Tumor-infiltrating Lymphocytes in Diffuse Large B-Cell Lymphoma

BACKGROUND: Programmed death-1 (PD-1) is physiologically expressed by germinal center-associated helper T-cells and has an inhibitory effect on T-cell activity. METHODS: We examined 63 cases of diffuse large B-cell lymphoma (DLBCL) and determined the number of PD-1-positive helper T-cells in a representative tumor area after immunohistochemical staining using a monoclonal antibody against PD-1. The PD-1-positive cells were counted in 3 high-power fields (HPFs; 400x). RESULTS: Patients were divided into 2 groups: one with a high number of PD-1-positive cells (>20/HPF, n=33) and one with a low number of PD-1-positive cells (< or =20/HPF, n=30). The former group showed decreased overall survival, but at a statistically non-significant level (p=0.073). A high number of PD-1-positive cells was more common in patients at an advanced clinical stage and with high international prognostic index score (p=0.025 and p=0.026, respectively). The number of extranodal sites also somewhat correlated with the PD-1 staining status (p=0.071). However, the number of PD-1-positive cells was not associated with patient age, serum lactate dehydrogenase level, and Eastern Cooperative Oncology Group performance score. CONCLUSIONS: The high number of PD-1-positive cells might be associated with an unfavorable outcome in DLBCL patients.