CD137, an attractive candidate for the immunotherapy of lung cancer

Lingyun Ye, Keyi Jia, Lei Wang, Wei Li, Bin Chen, Yu Liu, Hao Wang, Sha Zhao, Yayi He, Caicun Zhou, Lingyun Ye, Keyi Jia, Lei Wang, Wei Li, Bin Chen, Yu Liu, Hao Wang, Sha Zhao, Yayi He, Caicun Zhou

Abstract

Immunotherapy has become a hotspot in cancer therapy in recent years. Several immune checkpoints inhibitors have been used to treat lung cancer. CD137 is a kind of costimulatory molecule that mediates T cell activation, which regulates the activity of immune cells in a variety of physiological and pathological processes. Targeting CD137 or its ligand (CD137L) has been studied, aiming to enhance anticancer immune responses. Accumulating studies show that anti-CD137 mAbs alone or combined with other drugs have bright antitumor prospects. In the following, we reviewed the biology of CD137, the antitumor effects of anti-CD137 Ab monotherapy and the combined therapy in lung cancer.

Keywords: CD137; CD137L; anti-CD137 monoclonal antibody; immune therapy; lung cancer.

Conflict of interest statement

There were no conflicts of interest.

© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Figures

Figure 1
Figure 1
Role of CD137 and CD137 ligand (CD137L) signaling pathway. The interaction of CD137 with CD137L on activated antigen presenting cells (APC) contributes to the survival and activation of T cells. The CD137L signaling pathway can influence the activation, proliferation, and differentiation of CD137L expressing cells
Figure 2
Figure 2
Immune regulation mechanisms of anti‐CD137 mAb. Agonistic anti‐CD137 mAb can promote the activation, proliferation, and differentiation of CD8+ T cells, and enhance their cytolytic effect on tumor cells. Anti‐CD137 mAb acts on CD4+ T cells, leading to the release of cytokines useful to the activation and maturation of CD8+ T cells. Anti‐CD137 mAb can enhance the antibody dependent cell‐mediated cytotoxicity (ADCC) of natural killer (NK) cells and promote their proliferation and γ‐interferon (IFN‐γ) production. In addition, anti‐CD137 mAb can promote the activation and proliferation of dendritic cells (DCs). In regulatory T cells (Tregs), anti‐CD137 mAb can depress their function to enhance the antitumor effect. He et al41 provides some information, but does not include the effect of CD4+ T cells on CD8+ T cells, the effect of NK cells on CD8+ T cells, nor the effect of IFN‐γ

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