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Review
. 2017 May 31;8(57):97671-97682.
doi: 10.18632/oncotarget.18311. eCollection 2017 Nov 14.

Soluble PD-1 and PD-L1: predictive and prognostic significance in cancer

Xinxin Zhu  1 , Jinghe Lang  1
Affiliations
Review

Soluble PD-1 and PD-L1: predictive and prognostic significance in cancer

Xinxin Zhu et al. Oncotarget. .

Abstract

The membrane-bound molecules programmed death 1 (PD-1) and its ligand PD-L1 (PD-1/PD-L1) belong to the immune checkpoint pathway. PD-1 pathway downregulates effector T cells in immune response, thereby causing immune suppression. Recent studies have revealed that membrane-bound PD-1 and PD-L1 also have soluble forms. These soluble forms increase the complexity and diversity of the composition and function of the PD-1/PD-L1 signaling pathway. However, the exact roles of these molecules remain unknown. The objective of this systematic review was to elucidate the biological significance of soluble PD-1/PD-L1 in human cancers and evaluate whether they are potential diagnostic, therapeutic, or prognostic biomarkers. We expect to provide new clues for future research on soluble PD-1/PD-L1 pathway in human malignant tumors.

Keywords: PD-1; PD-L1; biomarker; soluble; tumor immunity.

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Conflict of interest statement

CONFLICTS OF INTEREST No potential conflict of interest relevant to this article is reported.

Figures

Figure 1
Figure 1. The inhibitory signaling of PD-1 pathway
(A) In B cells, PD-1 ligation along with BCR signaling leads to the phosphorylation of the tyrosine residue in ITSM. The phosphorylated tyrosine residue in ITSM recruits SHP-2. Thereafter, SHP-2 dephosphorylates BCR-proximal signaling molecules, including Syk, which attenuate the activation of downstream molecules. (B) In T cells, PD-1 ligation along with TCR signaling results in the phosphorylation of the tyrosine residue in ITSM and recruits SHP-2. The recruitment of SHP-2 dephosphorylates signaling through the PI3K or Zap70 pathways and inhibits of downstream signaling. Meanwhile, blockade of PI3K activation and the subsequent downregulation of IL-2 further induces CD8+ and CD4+ T-cell anergy.
Figure 2
Figure 2. Different PD-1 splice variants
Five splice variants of PD-1 mRNA transcripts have been cloned from human peripheral blood mononuclear cells: flPD-1, PD-1 Deltaex2, PD-1 Deltaex3, PD-1 Deltaex2,3, and PD-1 Deltaex2,3,4.
Figure 3
Figure 3. The blocking function of sPD-1
sPD-1 promotes T cell responses through blocking the following three interactions: PD-L1:B7-1, PD-L1:PD-1, and PD-L2:PD-1.
See this image and copyright information in PMC

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