Abstract
Binding of programmed cell death ligand 1 (PD-L1) to its receptor programmed cell death protein 1 (PD-1) can lead to the inactivation of cytotoxic T lymphocytes, which is one of the mechanisms for immune escape of tumors. Immunotherapy based on this mechanism has been applied in clinic with some remaining issues such as drug resistance. Exosomal PD-L1 derived from tumor cells is considered to play a key role in mediating drug resistance. Here, the effects of various tumor-derived exosomes and tumor-derived exosomal PD-L1 on tumor progression are summarized and discussed. Researchers have found that high expression of exosomal PD-L1 can inhibit T cell activation in in vitro experiments, but the function of exosomal PD-L1 in vivo remains controversial. In addition, the circulating exosomal PD-L1 has high potential to act as an indicator to evaluate the clinical effect. Moreover, therapeutic strategy targeting exosomal PD-L1 is discussed, such as inhibiting the biogenesis or secretion of exosomes. Besides, some specific methods based on the strategy of inhibiting exosomes are concluded. Further study of exosomal PD-L1 may provide an effective and safe approach for tumor treatment, and targeting exosomal PD-L1 by inhibiting exosomes may be a potential method for tumor treatment.
Highlights
Programmed cell death protein ligand 1 (PD-L1) is a type I transmembrane protein, which is expressed in many cell types including a variety of tumor cells
Liu and colleagues found that gastric cancer (GC) tumor cell-derived exosomes resulted in immunosuppressive tumor microenvironments in the lungs of mice, with increased CD4+ T cell and myeloid-derived suppressor cell (MDSC)
Current studies on the function of exosomal programmed cell death ligand 1 (PD-L1) derived from melanoma [5], gastric cancer [31], non-small cell lung cancer [32,33], osteosarcoma [34], and other tumors have demonstrated that exosomal PD-L1 could inhibit T cell activity and accelerate tumor growth through interaction with PD-1 in vitro
Summary
Programmed cell death protein ligand 1 (PD-L1) is a type I transmembrane protein, which is expressed in many cell types including a variety of tumor cells. Recent evidence suggests that tumor-derived exosomes may be responsible for immunosuppression of the tumor microenvironment and resistance to anti-PD-L1/PD-1 immune checkpoint therapy [3]. Ning et al reported that tumor exosome-treated dendritic cells (DCs) could inhibit CD4+ T cell proliferation and differentiation. Tumor cell-derived exosomes can indirectly DCs inhibit antibe partially reversed [6]. Tumor cell-derived exosomes can indirectly inhibit tumor immunity by up-regulating the expression of PD-L1 on various immune cells in the anti-tumor immunity by up-regulating the expression of PD-L1 on various immune cells tumor microenvironment, thereby creating suitable conditions for the growth of tumor in the tumor microenvironment, thereby creating suitable conditions for the growth of cells, a microenvironment with failed immunity.
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