Abstract
Non-small cell lung cancer is one of the most common types of malignances worldwide and the main cause of cancer-related deaths. Current treatment for NSCLC is based on surgical resection, chemotherapy, radiotherapy, and targeted therapy, with poor therapeutic effectiveness. In recent years, immune checkpoint inhibitors have applied in NSCLC treatment. A large number of experimental studies have shown that immune checkpoint inhibitors are safer and more effective than traditional therapeutic modalities and have allowed for the development of better guidance in the clinical treatment of advanced NSCLC patients. In this review, we describe clinical trials using ICI immunotherapies for NSCLC treatment, the available data on clinical efficacy, and the emerging evidence regarding biomarkers.
Highlights
The above studies have confirmed that people with high programmed cell death ligand 1 (PD-L1) expression can benefit from immune monotherapy, this group of patients accounts for a low percentage of non-small cell lung cancer (NSCLC), and how to expand the population benefiting from immunotherapy and obtain longer survival will be the focus of future research
Sacha et al studied the effect of durvalumab combined with chemotherapy in NSCLC (SAKK 16/14) [44]; the results showed that the addition of perioperative durvalumab to neoadjuvant chemotherapy in patients with stage IIIA(N2) NSCLC is safe and exceeds the historical data of chemotherapy alone, with a high MPR and an encouraging one-year event-free survival (EFS) rate of 73%
Matthew et al further confirmed that first-line treatment with nivolumab plus ipilimumab resulted in a longer duration of overall survival (OS) than did chemotherapy in NSCLC patients, independent of their PD-L1 expression level (CheckMate 227) [58]
Summary
The growth and spread of malignant tumors are a complex process that depends on the characteristics of the tumor cells but is influenced by the immune system [8], and the occurring of immune escape is a very important step for tumorigenesis. The main reason is that the cytoplasmic region of CTLA-4 includes an immunoreceptor tyrosine-based inhibitory motif (ITIM) that transmits inhibitory signals This effect weakens the immune response and contributes to the escape of tumor cells. High expression of PD-L1 results in immune escape, as in lung cancer, where PD-L1 is expressed in 35–95% of NSCLC patients [13]. High expression of PD-L1 in lung cancer tissues is often accompanied by high levels of T cell infiltration, which often means depletion of T cells and their antitumor effects. This is the strategy used by lung cancer cells to avoid detection by immune system surveillance and, elimination [15]. We discuss the clinical efficacy, safety, therapeutic strategies, challenges, and expectations of drugs related to the treatment of NSCLC with PD-1/PD-L1 and CTLA-4 as targets
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