Evolution of Lung Cancer in the Context of Immunotherapy

Abstract

Immunotherapy, as a novel treatment, has brought new hope to many patients with cancer, including patients with lung cancer. However, the overall cure rate and survival rate of lung cancer are still not satisfactory. The process of evolution has improved the ability of tumors to adapt to immunotherapy, which induces drug resistance. Many studies have focused on immunoresistance and achieved meaningful results. Therefore, it is necessary to have an in-depth understanding of the current research progress in immunoresistance, which will help to achieve good clinical results more efficiently.

Keywords: Lung cancer; cancer evolution; drug resistance; immunotherapy.

Figure 1.

Blockade of CTLA-4 and of PD-1 and PD-L1 to induce antitumor responses. CTLA-4 and PD-1 are both inhibitory immunocheckpoint, and their activation can turn off the antitumor T cell responses. The activation of CTLA-4 can be blocked with anti-CTLA-4 antibodies. The activation of PD-1 can be blocked by anti-PD-1 or anti-PD-L1 antibodies. APC indicates antigen-presenting cell; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; MHC, major histocompatibility complex; PD-1, programmed death 1; PD-L1, programmed death ligand-1; TCR, T-cell receptor.

Figure 2.

Summary of resistance factors of PD-1/PD-L1. Tumor resistance to PD-1/PD-L1 immunotherapy is mainly related to the influence of the 2 aspects in the figure, each of which can be subdivided into multiple factors to form an interwoven network of mutual influence. Combined multitarget therapy can improve the tumor response rate. The combination of multiple drugs and the development of new drugs are current trends. ALK indicates anaplastic lymphoma kinase; B2M, β-2-microglobulin; BTLA, B- and T-lymphocyte attenuator; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; EGFR, epidermal growth factor receptor; IDO, indoleamine 2,3-dioxygenase; IFN-γ, interferon-gamma; JAK/STAT, Janus kinase/signal transducer and activator of transcription; LAG-3, lymphocyte activation gene 3; MDSC, myeloid suppressor cells; MHC, major histocompatibility complex; NKG2D, natural killer group 2, member D; PD-1, programmed death 1; PD-L1, programmed death ligand-1; PI3K/Akt, phosphatidylinositol-3 kinase/serine-threonine kinase; PTEN, phosphatase and tensin homolog; RAS/MAPK, RAS-mitogen-activated protein kinase; TGF, transforming growth factor; TIGIT, T cell immunoglobulin and ITIM domain; TIM3, T cell immunoglobulin mucin 3; Treg, tumor-infiltrating regulatory T cell; VEGF, vascular endothelial growth factor.