Towards the development of next-generation lung cancer immunotherapy

Abstract

The immune system attempts to eliminate foreign substances, such as pathogens and viruses, that invade the body. As normal cells transform into cancerous cells, the immune system can eliminate these cells and suppress cancer onset. The immune system is regulated so that it does not become overactive or attack normal cells. When cancer cells transform from normal cells, they acquire various characteristics, and some cancer cells influence the regulatory function of the immune system to suppress it and escape immune attack. Therefore, treatments have been developed to eliminate the suppression of the immune system by cancer cells and to restore the immune system's ability to eliminate cancer cells. Immunotherapies include immune checkpoint inhibitors, cytokines, cancer vaccines, and effector cell therapies. Cytokine therapy activates the immune system by injecting substances produced by immune cells (such as interleukin 2 and interferon alpha) into the body, thereby increasing the ability of the immune system to attack cancer cells. Cancer vaccine therapy enhances the attack on cancer cells by injecting substances (antigens) that serve as markers for cancer cells into the body to make it easier for immune cells to detect the cancer. Depending on the type of antigen, cancer peptides, tumor cells, and dendritic cell vaccines are available. Effector cell therapy is a treatment method in which immune cells that directly attack cancer cells [CD8⁺ T cells, natural killer (NK) cells, etc.] are taken from the patient's body, expanded outside the body, activated, and returned to the body to attack cancer cells. To develop these treatments, it is essential to understand the cells and molecules related to immunity as well as the local tumor environment. In this article, we consider the factors related to antitumor immunity.

Keywords: Lung cancer; cancer immunology; cytotoxic T lymphocyte (CTL); immune check inhibitor (ICI).

Figure 1

Immune cells involved in antitumor immunity. There are various immune cells involved in anti-tumor immunity. There are interactions, and the functions of individual immune cells can vary, making understanding difficult. Nevertheless, it is necessary to develop next-generation cancer immunotherapy by understanding the basic characteristics of each immune cell. ADCC, antibody dependent cellular cytotoxicity; CDC, complement dependent cytotoxicity; MDSC, myeloid-derived suppressor cells; CAF, cancer-associated fibroblast.

Figure 2

Chimeric antigen receptor-T cells (CAR-T cells). The components of CAR-T cells consist of a single-chain antibody (single-chain antibody variable fragment, scFV), a flexible connecting chain (hinge), a transmembrane domain and the signaling domains of the costimulatory molecule CD28, 4-1BB or OX-40 and stimulatory molecule CD3ζ and FcRγchain.