Identification of CD112R as a novel checkpoint for human T cells

Zhu, Yuwen; Paniccia, Alessandro; Schulick, Alexander; Chen, Wei; Koenig, Michelle R.; Byers, Joshua T.; Yao, Sheng; Bevers, Shaun; Edil, Barish H.

doi:10.1084/jem.20150785

Cited by 164 publications

(199 citation statements)

References 30 publications

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“…Adaptive immunity, mainly mediated by T cells, is known to be essential for trastuzumab therapy of breast cancer [23,24]. Besides NK cells, TIGIT and CD112R are also known to be key checkpoints for T cells [17,25]. Although our studies here only address the role of NK cell-mediated antitumor response in trastuzumab therapy, the effect of PVR-like checkpoint inhibitor on promoting T cell-mediated adaptive antitumor immunity remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Anti-human CD226 mAb (clone DX11, mouse IgG1) was purchased from Abcam. Mouse anti-human CD112R mAb (clone 2H6, IgG1) was generated from a hybridoma derived from the fusion of SP2 myeloma with B cells from a mouse immunized with human CD112R-Fc [17]. LEAF ™ (Low Endotoxin, Azide-Free) purified mouse IgG1 (clone MG1-45), used for isotype control in culture, was obtained from BioLegend.…”

Section: Methodsmentioning

confidence: 99%

“…CD155, but not CD112, interacts with CD96, another PVR-like co-receptor present on T cells and NK cells, though the function of this interaction is still unclear [14,15,16]. Adding to the complexity of this network, we recently identified CD112R as a new inhibitory receptor of the PVR-like family, which interacts with CD112, but not CD155 [17]. CD112R is expressed on human NK cells, though its function on this cell type is unclear.…”

Section: Introductionmentioning

confidence: 99%

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Blockade of CD112R and TIGIT signaling sensitizes human natural killer cell functions

Sunderland

Zhou

et al. 2017

Cancer Immunol Immunother

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Trastuzumab is the first-line drug to treat breast cancer with high Her2 expression. However, many cancers failed to respond, largely due to their resistance to NK cell-triggered antibody-dependent cellular cytotoxicity (ADCC). Poliovirus receptor (PVR)-like molecules are known to be important for lymphocyte functions. We found that all PVR-like receptors are expressed on human NK cells, and only TIGIT is preferentially expressed on the CD16+ NK cell subset. Disrupting the interactions of PVR-like receptors with their ligands on cancer cells regulates NK cell activity. More importantly, TIGIT is upregulated upon NK cell activation via ADCC. Blockade of TIGIT or CD112R, separately or together, enhances trastuzumab-triggered antitumor response by human NK cells. Thus, our findings suggest that PVR-like receptors regulate NK cell functions and can be targeted for improving trastuzumab therapy for breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Blockade of CD112R and TIGIT signaling sensitizes human natural killer cell functions

Sunderland

Zhou

et al. 2017

Cancer Immunol Immunother

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128

101

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“…The network is completed by the co-inhibitory receptors CD96 (Tactile), an additional binding partner for CD155, and CD112R, which interacts with CD112 (Fig. 2a) (Chan et al 2014; Fuchs et al 2004; Zhu et al 2016). …”

Section: Tigitmentioning

confidence: 99%

Tim-3, Lag-3, and TIGIT

Joller

Kuchroo

2017

Current Topics in Microbiology and Immunology

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Co-inhibitory receptors play a key role in regulating T cell responses and maintaining immune homeostasis. Their inhibitory function prevents autoimmune responses but also restricts the ability of T cells to mount effective immune responses against tumors or persistent pathogens. T cells express a module of co-inhibitory receptors, which display great diversity in expression, structure, and function. Here, we focus on the co-inhibitory receptors Tim-3, Lag-3, and TIGIT and how they regulate T cell function, maintenance of self-tolerance, their role in regulating ongoing T cell responses at peripheral tissues, and their synergistic effects in regulating autoimmunity and antitumor responses.

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“…CD112 is another TIGIT ligand with lower binding affinity than CD155 [46,47]. Here we showed that CD112 was moderately expressed on self-cells such as macrophages, DCs, granulocytes and monocytes (Fig.…”

Section: Tigit þ Nk Cells Are Rendered Hypo-responsive In Cd155-deficmentioning

confidence: 75%

Contribution of inhibitory receptor TIGIT to NK cell education

Peng

Sun

et al. 2017

Journal of Autoimmunity

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Identification of CD112R as a novel checkpoint for human T cells

Abstract: Zhu et al. report the identification of CD112R as a new coinhibitory receptor of the TIGIT–DNAM-1 family for human T cells.

Cited by 164 publications

References 30 publications

Blockade of CD112R and TIGIT signaling sensitizes human natural killer cell functions

Blockade of CD112R and TIGIT signaling sensitizes human natural killer cell functions

Tim-3, Lag-3, and TIGIT

Contribution of inhibitory receptor TIGIT to NK cell education

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