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Mechanisms of primary and acquired resistance to PD-1/PD-L1 blockade and the emerging role of gut microbiome

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Abstract

As a very promising immunotherapy, PD-1/PD-L1 blockade has revolutionized the treatment of a variety of tumor types, resulting in significant clinical efficacy and lasting responses. However, these therapies do not work for a large proportion of patients initially, which is called primary resistance. And more frustrating is that most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade. The mechanisms that lead to primary and acquired resistance to PD-1/PD-L1 inhibition have remained largely unclear. Recently, the gut microbiome has emerged as a potential regulator for PD-1/PD-L1 blockade. This review elaborates on the current understanding of the mechanisms in terms of PD-1 related signaling pathways and necessary factors. Moreover, this review discusses new strategies to increase the efficacy of immunotherapy from the perspectives of immune markers and gut microbiome.

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  1. R. Zou and Y. Wang have contributed equally to this work.

  2. S. Cui should be regarded as a joint first author for her equal contributions.

Authors and Affiliations

  1. The First School of Clinical Medicine, Nanjing Medical University, Nanjing, 210029, Jiangsu, China

    R. Zou, Y. Wang, F. Ye, X. Zhang & M. Wang

  2. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China

    S. Cui

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  1. R. Zou
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  4. X. Zhang
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All authors contributed to the study conception and design. The literature search and data analysis were performed by FY, XZ and MW. The first draft of the manuscript was written by RZ and YW mainly drafted and critically revised the work. All authors read and approved the final manuscript.

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Zou, R., Wang, Y., Ye, F. et al. Mechanisms of primary and acquired resistance to PD-1/PD-L1 blockade and the emerging role of gut microbiome. Clin Transl Oncol 23, 2237–2252 (2021). https://doi.org/10.1007/s12094-021-02637-2

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