OncoTargets and Therapy (Oct 2019)

The Role Of PD-1/PD-L1 Axis In Treg Development And Function: Implications For Cancer Immunotherapy

  • Cai J,
  • Wang D,
  • Zhang G,
  • Guo X

Journal volume & issue
Vol. Volume 12
pp. 8437 – 8445

Abstract

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Jiajing Cai,1,* Dongsheng Wang,1,* Guoyuan Zhang,1 Xiaolan Guo1–3 1Department of Laboratory Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, People’s Republic of China; 2Department of Laboratory Medicine, North Sichuan Medical College, Nanchong, Sichuan 637000, People’s Republic of China; 3Translational Medicine Research Center, North Sichuan Medical College, Nanchong, Sichuan 637000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoyuan ZhangDepartment of Laboratory Medicine, Affiliated Hospital of North Sichuan Medical College, 63 Wenhua Road, Nanchong, Sichuan 637000, People’s Republic of ChinaTel/fax +86-817-2190089Email [email protected] GuoDepartment of Laboratory Medicine, North Sichuan Medical College, 234 Fujiang Road, Nanchong, Sichuan 637000, People’s Republic of ChinaTel/fax +86-817-2282052Email [email protected]: During the past decade, immunotherapy targeting immune checkpoints has become an important component of the treatment paradigm for numerous malignancies, especially PD-1/PD-L1 blockade which was demonstrated to rejuvenate disabled T cells in cancer patients to achieve long-term remissions. However, the clinical outcome of PD-1/PD-L1 targeted monotherapy against solid malignancies is not satisfactory which may be related with the intricate tumor microenvironment. As a vital suppressive immunocyte in tumor microenvironment, Tregs are characterized by PD-1 and PD-L1 and demonstrated to contribute to the tumor progression. The latest studies have suggested that Tregs might be involved in the treatment of PD-1/PD-L1 blockade and PD-1/PD-L1 axis could influence Treg differentiation and function. However, the complicated relationship between PD-1/PD-L1 pathway and Tregs has not been fully clarified. Here, we explored the role of PD-1/PD-L1 axis in Treg development and function, as well as the potential mechanisms of PD-1/PD-L1 blockade resistance related with Tregs. Meanwhile, we discussed the combination therapy aimed at targeting PD-1/PD-L1 axis and Tregs, hoping to provide novel insights for the future cancer treatment.Keywords: PD-1, PD-L1, tregs, CTLA-4, combination therapy

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