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

R. Zou ^[1] ; Y. Wang ^[1] ; F. Ye ^[1] ; X. Zhang ^[1] ; M. Wang ^[1] ; S. Cui ^[2]
1. [1] Nanjing Medical University
  
  Nanjing Medical University
  
  China
2. [2] Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China
Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 23, Nº. 11, 2021, págs. 2237-2252
Idioma: inglés
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Resumen
- s 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 immu- notherapy from the perspectives of immune markers and gut microbiome