Targeting programmed cell death protein 1 (PD-1) for treatment of non-small-cell lung carcinoma (NSCLC); the recent advances.

Abstract

The immune system uses various immune checkpoint axes to adjust responses, support homeostasis, and deter self-reactivity and autoimmunity. Nevertheless, non-small-cell lung carcinoma (NSCLC) can use protective mechanisms to facilitate immune evasion, which leads to potentiated cancer survival and proliferation. In this light, many blocking anti-bodies have been developed to negatively regulate checkpoint molecules, in particular, programmed cell death protein 1 (PD-1) / PD-ligand 1 (L1), and bypass these immune suppressive mechanisms. Meanwhile, anti-PD-1 anti-bodies such as nivolumab, pembrolizumab, cemiplimab, and sintilimab have shown excellent competence in successfully inspiring immune responses versus NSCLC. Accordingly, the United States Food and Drug Administration (FDA) has recently approved nivolumab (alone or in combination with ipilimumab) and pembrolizumab (alone or in combination with chemotherapy) as first-line treatment for advanced NSCLC patients. However, PD-1 blockade monotherapy remains inefficient in more than 60% of NSCLC patients, and many patients don't respond or acquire resistance to this modality. Also, toxicities related to anti-PD-1 anti-body have been progressively identified in clinical trials and oncology practice. Herein, we will outline the clinical benefits of PD-1 blockade therapy alone or in combination with other treatments (e.g., chemotherapy, radiotherapy, anti-angiogenic therapy) in NSCLC patients. Moreover, we will take a glimpse into the recently identified predictive biomarkers to determine patients most likely to suffer serious adverse events to decrease untoward toxicity risk and diminish treatment costs.