Poliovirus receptor (PVR)-like protein cosignaling network: new opportunities for cancer immunotherapy

Wu, Baokang; Zhong, Chongli; Lang, Qi; Liang, Zhiyun; Zhang, Yizhou; Zhao, Xin; Yu, Yang; Zhang, Heming; Xu, Feng; Tian, Yu

doi:10.1186/s13046-021-02068-5

Journal of Experimental & Clinical Cancer Research

Table 1 Preclinical trials in promising cancer target of PVR like receptors

From: Poliovirus receptor (PVR)-like protein cosignaling network: new opportunities for cancer immunotherapy

PVR like protein	Treatment	Immune cells	Tumor	Results	Reference
DNAM-1	Anti-DMAN-1 or anti-PVR mAbs	NK	Neuroblastoma	monoclonal antibody-mediated masking of either DNAM-1 (on NK cells) or PVR (on neuroblasts) resulted in strong inhibition of tumor cell lysis	[26]
DNAM-1	Anti-DMAN-1 or anti-PVR mAbs	NK	Tumor cell lines	The ability of NK-mediated lysis of tumor cells mediated by DNAM-1 engage with its ligands that was downregulated by mAb-mediated masking of the receptor or its ligands	[15]
DNAM-1	anti-CD226 mAb LeoA1	NK	Hepatoma	Crosslinking CD226 with the anti-CD226 mAb LeoA1 regulate miR-30c-1* expression, which promoted NK cell cytotoxicity against hepatoma cells by targeting HMBOX1	[27]
DNAM-1	DNAM-1 agonist	NK	Melanoma, experimental autoimmune encephalomyelitis	DNAM-1 agonist could activate DNAM-1 modifies the bidirectional crosstalk of NK cells with CD155 DC, which can suppress CNS autoimmunity and strengthen tumor surveillance	[28]
DNAM-1	Anti-CD226 mAb	Tregs	Allogeneic skin transplant	CD226 mAb promoted Treg expansion, reduced inflammation and prolonged allogeneic graft survival	[29]
DNAM-1	Anti-CD226 mAb	γδT	Hepatocellular carcinoma	Anti-DNAM-1 mAb-mediated masking experiments that γδT cells cytotoxicity against HCC cells as well as IFN-γ production were decreased	[30]
DNAM-1	CD226 agonist antibody	CD8+ T	pancreatic ductal adenocarcinoma	CD226 agonist antibody-mediated activation of CD226 augments the effect of TIGIT or PD-1 blockade on CD8 T-cell responses	[31]
TIGIT	Anti-TIGIT	NK	Colon cancer	Blockade of TIGIT prevented NK cell exhaustion and promoted NK cell–dependent tumor immunity, enhanced therapy with antibody to the PD-1 ligand PD-L1	[32]
TIGIT	Anti-TIGIT	NK	Ovarian cancer	Blockade of TIGIT enhanced degranulation and interferon gamma (IFN-γ) production of NK cells in response to OC tumor cells	[33]
TIGIT	Anti-TIGIT	CD8+ T	Melanoma	TIGIT and PD-1 blockade should be further explored to elicit potent antitumor CD8+ T cell responses	[34]
TIGIT	Anti-TIGIT	CD8+ T	Gastric cancer	Blockade TIGIT enhanced CD8 T cell activation and improved survival in tumor bearing mice	[35]
TIGIT	Anti-TIGIT	CD8+ T	Multiple myeloma	Blockade TIGIT by mAb increased the effector function of MM patient CD8+ T cells and suppressed MM development	[36]
TIGIT	Anti-TIGIT	CD8+ T	Myeloma	Immune checkpoint blockade using mAb against TIGIT significantly restored CD8+ T exhaustion and prolonged myeloma control after stem cell transplantation	[37]
TIGIT	Anti-TIGIT	CD8+ T, Tregs	Head and neck squamous cell carcinoma	Anti-TIGIT treatment significantly reverse T-cell exhaustion and reduce the population of Tregs in vitro and in vivo	[38]
TIGIT	Anti-TIGIT	CD4+ T, CD8+ T, Tregs	Multiple myeloma	Anti-TIGIT mAb depleted FoxP3+ Tregs, increased proliferation of IFN-γ-producing CD4+ T cells, and overcame the inhibition effect of CD8+ T cell signaling and cell proliferation by PVR ligation	[39]
TIGIT	Anti-TIGIT	αβT, γδT, Tregs	Hematologic malignancies	Anti-TIGIT mAbs could restore αβT-cell function, prevent CD155 mediated inhibition of γδ T cells, depletion of Tregs, and direct killing of tumor cells	[40]
TIGIT	Anti-TIGIT	Effector T, Tregs	Glioblastoma	TIGIT a checkpoint blockade increased effector T cell function and downregulation of suppressive Tregs and TIDCs to enhance antitumor immunity and survival in glioblastoma	[41]
TIGIT	Anti-TIGIT	CD4+ Tregs	Ovarian cancer	Anti-TIGIT treatment reduced the proportion of CD4+ Tregs	[42]
CD96	Anti-CD96	NK	Melanoma lung metastases	Anti-CD96 enhances the NK cell IFN-γ-dependent effector function, which significantly reduced experimental and spontaneous lung metastases	[43]
CD96	Anti-CD96	NK	Hepatocellular carcinoma	Anti-CD96 antibody of blocking CD96 and its ligand CD155 interaction, the human NK cell lines cytotoxicity was restored and enhanced	[44]
CD96	Anti-CD96	NK	Tumor metastases	CD96 targeted antibodies promote NK cell anti-tumor activity	[45]
CD96	Anti-CD96	CD8+ T	Anti-tumor	Ab blockade on CD8+ T cells could eliminate IFN-γ and/or TNF-α production, which associated with CD8+ T cell activation	[46]
CD96	Anti-CD96	CD8+ T	Melanoma	Anti-CD96 therapy is effective to enhance CD8+ T activity and limit tumor growth	[47]
CD96	Anti-CD96	Th19	Inflammatory diseases	Blockade of CD96 significantly restored the expansion and inflammatory properties of CD96^high Th9 cells	[48]
CD112R	Anti-CD112R	NK	Breast cancer	Blockage CD112R could improve trastuzumab therapy for breast cancer by enhancing NK cells activity	[49]
CD112R	Anti-CD112R	CD8+ T	Melanoma, pancreatic cancer	Blockade of PVRIG increased CD8+ T-cell function, an effect enhanced by combination with TIGIT or PD-1 blockade	[50]

mAb monoclonal antibody, CNS central nervous system, HCC hepatocellular carcinoma, PD-1 programmed cell death 1, PD-L1 programmed cell death-ligand 1, TIDCs tumor-infiltrating dendritic cells

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