RESUMEN

Lymphocyte activation gene 3 (LAG-3), also known as CD223, is an emerging immune checkpoint that follows PD-1 and CTLA-4. Several LAG-3 targeting inhibitors in clinical trials and the combination of relatlimab (anti-LAG-3) and nivolumab (anti-PD-1) have been approved for treating - unresectable or metastatic melanoma. Despite the encouraging clinical potential of LAG-3, the physiological function and mechanism of action in tumors are still not well understood. In this review, we systematically summarized the structure of LAG-3, ligands of LAG-3, cell-specific functions and signaling of LAG-3, and the current status of LAG-3 inhibitors under development.

RESUMEN

PURPOSE: Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients. MATERIALS AND METHODS: Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m2 nab-paclitaxel, 800 mg/m2 gemcitabine, and 25 mg/m2 cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy. RESULTS: After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients' survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1-positive (PD-1+) cells (p=0.032) were observed in the response patients. CONCLUSION: In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.

Asunto(s)

Albúminas , Neoplasias de los Conductos Biliares , Paclitaxel , Neoplasias Pancreáticas , Humanos , Gemcitabina , Cisplatino/efectos adversos , Desoxicitidina/efectos adversos , Antígeno Carcinoembrionario/uso terapéutico , Receptor de Muerte Celular Programada 1 , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Pancreáticas/patología

RESUMEN

The tumor microenvironment (TME) plays a vital role in the development, progression, and metastasis of pancreatic cancer (PC). The composition of the TME and its potential prognostic value remains to be fully understood, especially in adenosquamous carcinoma of pancreas (ASCP) patients. Immunohistochemistry was used to explore the clinical significance of CD3, CD4, CD8, FoxP3, and PD-L1 expression within the TME and to identify correlations with the prognosis of PC in a series of 29 patients with ASCP and 54 patients with pancreatic ductal adenocarcinoma (PDAC). Data from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) were accessed to obtain the scRNA-seq data and transcriptome profiles. Seurat was used to process the scRNA-seq data, and CellChat was used to analyze cell-cell communication. CIBERSORT was used to approximate the constitution of tumor-infiltrating immune cell (TICs) profiles. Higher levels of PD-L1 were linked with a shorter overall survival in ASCP (p = 0.0007) and PDAC (p = 0.0594). A higher expression of CD3+ and CD8+ T-cell infiltration was significantly correlated with a better prognosis in PC. By influencing the composition of tumor-infiltrating immune cells (TICs), high levels of PD-L1 expression are linked with a shorter overall survival in ASCP and PDAC.

RESUMEN

BACKGROUND: About 80% lung cancer is non-small cell lung cancer (NSCLC) and 70%-80% are in advanced stage. Chemotherapy is main treatment method. The aim of this study is to compare the therapeutic effects and toxicity of NP regimen combined with Shenqifuzheng injection on elder patients with advanced NSCLC. METHODS: Totally 69 patients enrolled into this study and were randomized into two groups: treatment group (35 patients) and control group (34 patients). Each patient received NVB 25mg/m² intravenously at days 1 and 8 and DDP 30mg intravenously from 1st day to 4th day. Shenqifuzheng injection was used in the treatment group by 250mL per day for 10 days. RESULTS: There was no significant difference of the response rate between two groups (45.7% vs 41.2%, P > 0.05). The hematological toxicity, nausea and vomiting in the treatment group were lower than those in the control group with significant difference (P < 0.05). The adverse effects were well tolerable. CONCLUSIONS: NP regimen combined with Shenqifuzheng injection on elder patients with advanced NSCLC is effective and safe. Shenqifuzheng injection has definite toxicity relieving effect on treating elder patients with advanced NSCLC.