Real-World Clinical Impact of Immune Checkpoint Inhibitors in Patients With Advanced/Metastatic Non-Small Cell Lung Cancer After Platinum Chemotherapy

Lung cancer is the first most common malignancy in the wild word, and the leading cause of cancer-related mortality. Approximately 85% of lung cancers are non-small-cell lung cancer (NSCLC). More than half of all lung cancers in the United States are diagnosed at advanced or metastatic stage, which has a 5-year survival of 4.8%. The recommendations for systemic treatment of metastatic NSCLC (stage IV) are guided by patient performance status (PS), tumor histology, and status of tumor biomarkers. Firstline (1L) treatment with platinum-based chemotherapy has long been the standard of care. In the second-line (2L) setting after 1L chemotherapy, the efficacy and safety of antiePD-L1 therapies have been shown in several phase III clinical trials.

Notebook: Prophylactic TNF blockade uncouples efficacy and toxicity in dual CTLA-4 and PD-1 immunotherapy

Immunotherapy combined with PD-1 and CTLA-4 is effective for renal melanoma and non-small cell lung cancer.However, thiscomes at the cost of frequent, serious immune-related adverseevents, necessitating a reduction in the recommended dose ofipilimumab that is given to patients. Immune-related adverse events that result from therapy with checkpoint inhibitors are usually satisfactorily treated by discontinuing theuse of the therapeutic agents and beginning a course of steroids. However, after stopping the use of checkpoint inhibitors, the tumor could not be treated.

Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response

Tumor cells evade immune surveillance by upregulating the surface expression of programmed death-ligand 1 (PD-L1), which interacts with programmed death-1 (PD-1) receptor on T cells to elicit the immune checkpoint response. Anti-PD-1 antibodies have shown remarkable promise in treating tumors, including lung cancer and metastatic melanoma. However, there is a problem that PD-1/PD-L1 blockade is associated with a response rate is low. A better understanding of PD-L1-mediated immune evasion is needed to predict patient response and improve treatment efficacy.