Immunotherapy in non-small cell lung cancer: the clinical impact of immune response and targeting

Abstract

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. In recent years, through a better understanding of the interactions between the immune system and tumor cells (TC), immunotherapy has emerged as a promising therapeutic strategy. Chemotherapy has long been reported to interfere with the immune response to the tumor and conversely, anti-tumor immunity may add to those effects. Anti-tumor vaccines, such as MAGE-A3, Tecetomide, TG4010, CIMAvax, tumor cell vaccines and dendritic cell (DC) vaccines emerged as potent inducers of the immune response against the tumor. More recently the approval of the anti-programmed cell death 1 (anti-PD-1) monoclonal antibodies nivolumab and pembrolizumab for previously treated advanced squamous and non-squamous NSCLC, as well as other immune checkpoint inhibitors delivering promising results, has radically transformed the therapeutic landscape of NSCLC. Combination strategies now appear as the next step. Notwithstanding these successes, immunotherapy still holds significant drawbacks and currently several improvements are needed before routine use in clinical practice, including identification of robust biomarkers for optimal patient selection, as well as defining the best way to evaluate response.

Keywords: Non-small cell lung cancer (NSCLC); checkpoint inhibitors; immunotherapy; vaccines.

Figure 1

Cancer cells interactions with their microenvironment’s immune system. APC, antigen-presenting cell; CTL, cytotoxic T lymphocyte; IDO, indoleamine 2,3-dioxygenase; MDSC, myeloid-derived suppressor cell; PNT, peroxynitrite; TCR, T-cell receptor; MHC, major histocompatibility complex; PD-L1, programmed feath ligand 1; TGF-β, transforming growth factor-beta; VEGF, vascular endothelial growth factor.