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Small molecular drugs reshape tumor microenvironment to synergize with immunotherapy

Oncogene volume 40, pages 885–898 (2021)Cite this article

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Abstract

Recently, immune checkpoint blockade (ICB), especially anti-programmed death 1 (anti-PD-1) and anti-programmed death-ligand 1 (anti-PD-L1) therapy, has become an increasingly appealing therapeutic strategy for cancer patients. However, only a small portion of patients responds to anti-PD treatment. Therefore, treatment strategies are urgently needed to reverse the ICB-resistant tumor microenvironment (TME). It has become clear that the TME has diminished innate sensing that is critical to activate adaptive immunity. In addition, tumor cells upregulate various immunosuppressive factors to diminish the immune response and resist immunotherapy. In this review, we briefly update the current small molecular drugs that could synergize with immunotherapy, especially anti-PD therapy. We will discuss the modes of action by those drugs including inducing innate sensing and limiting immunosuppressive factors in the TME.

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Fig. 1: Methods of triggering innate sensing in the TME that can synergize with anti-PD therapy.
Fig. 2: Targeting immunosuppressive factors in the TME to provoke antitumor immunity.

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Acknowledgements

We thank members of Prof. Yang-Xin Fu lab for fruitful discussions. This work was supported by Cancer Prevention and Research Institute of Texas (CPRIT) grant RR150072 given to Y-XF.

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  1. The Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA

    Chuanhui Han, Anli Zhang, Zhida Liu, Casey Moore & Yang-Xin Fu

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Han, C., Zhang, A., Liu, Z. et al. Small molecular drugs reshape tumor microenvironment to synergize with immunotherapy. Oncogene 40, 885–898 (2021). https://doi.org/10.1038/s41388-020-01575-7

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