Tumor Immunology and Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer

Abstract

Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths worldwide. Although progress in the treatment of advanced non-small cell lung cancer (NSCLC) has been made over the past decade, the 5-year survival rate in patients with lung cancer remains only 10%-20%. Obviously, new therapeutic options are required for patients with advanced NSCLC and unmet medical needs. Cancer immunotherapy is an evolving treatment modality that uses a patient's own immune systems to fight cancer. Theoretically, cancer immunotherapy can result in long-term cancer remission and may not cause the same side effects as chemotherapy and radiation. Immuno-oncology has become an important focus of basic research as well as clinical trials for the treatment of NSCLC. Immune checkpoint inhibitors are the most promising approach for cancer immunotherapy and they have become the standard of care for patients with advanced NSCLC. This review summarizes basic tumor immunology and the relevant clinical data on immunotherapeutic approaches, especially immune checkpoint inhibitors in NSCLC.

Keywords: Carcinoma, Non-Small-Cell Lung; Cell Cycle Checkpoints; Immunotherapy.

Figure 1. The three phases of the cancer immunoediting process: elimination, equilibrium, and escape. DC: dendritic cell; γδ: γδ T cell; IDO: indoleamine 2,3-dioxygenase; IFN-γ: interferon γ; IL: interleukin; M1: M1 macrophage; M2: M2 macrophage; MDSC: myeloid-derived suppressor cell; NK: natural killer cell; NKT: natural killer T cell; PD-L1: programmed death ligand 1; TGF-β: transforming growth factor β; Treg: regulatory T cell. Modified from Schreiber et al. Science 2011;331:1565-70, with permission of The American Association for the Advancement of Science.

Figure 2. The cancer-immunity cycle. APC: antigen presenting cell; MHC: major histocompatibility complex; TCR: T cell receptors.

Figure 3. The immune system activation and checkpoint inhibitors. APC: antigen presenting cell; CTLA-4: cytotoxic T-lymphocyte-associated antigen 4; PD-1: programmed cell death protein 1; PD-L1: programmed death ligand 1; TCR: T cell receptors. Modified from Pardoll. Nat Rev Cancer 2012;12:252-64, with permission of Springer Nature.