Targeting PVR (CD155) and its receptors in anti-tumor therapy

Brlić, Paola Kučan; Roviš, Tihana Lenac; Cinamon, Guy; Tsukerman, Pinchas; Mandelboim, Ofer; Jonjić, Stipan

doi:10.1038/s41423-018-0168-y

Cited by 126 publications

(103 citation statements)

References 187 publications

(282 reference statements)

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“…Interestingly, the manifestation of Treg suppressive activity against a specific T effector population may be associated with the expression of transcription factors typical of this subpopulation. Thus, the expression of T-bet, a Th-1-associated transcription factor, in Tregs is related to the expression of the inhibitory molecule TIGIT, which binds CD155 to dendritic cells to increase the production of IL-10 and reduce that of IL-12 in the dendritic cell, thus inhibiting the activation of T effectors (60,61). Tregs with the T-bet + TIGIT + phenotype selectively inhibit the Th1and Th17-mediated proinflammatory immune response (62,63).…”

Section: Treg Suppressive Activity Mechanismsmentioning

confidence: 99%

Treg Heterogeneity, Function, and Homeostasis

2020

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Section: Treg Suppressive Activity Mechanismsmentioning

confidence: 99%

Treg Heterogeneity, Function, and Homeostasis

2020

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“…PVR (CD155) is a member of the immunoglobulin superfamily as well as being the fifth member of the nectin-like molecule family and is therefore also known as necl-5 (152). It is barely expressed in normal human tissues, but many tumor cell lines and primary malignancies highly express PVR (54,153). Of the functions performed by PVR, immunoregulation through its interaction with inhibitory receptors TIGIT and CD96 and activating receptor CD226 is of particular interest.…”

Section: Tigit and Cd96mentioning

confidence: 99%

NK Cell-Based Immune Checkpoint Inhibition

Arooj²,

2020

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Immunotherapy, with an increasing number of therapeutic dimensions, is becoming an important mode of treatment for cancer patients. The inhibition of immune checkpoints, which are the source of immune escape for various cancers, is one such immunotherapeutic dimension. It has mainly been aimed at T cells in the past, but NK cells are a newly emerging target. Simultaneously, the number of checkpoints identified has been increasing in recent times. In addition to the classical NK cell receptors KIRs, LIRs, and NKG2A, several other immune checkpoints have also been shown to cause dysfunction of NK cells in various cancers and chronic infections. These checkpoints include the revolutionized CTLA-4, PD-1, and recently identified B7-H3, as well as LAG-3, TIGIT & CD96, TIM-3, and the most recently acknowledged checkpoint-members of the Siglecs family (Siglec-7/9), CD200 and CD47. An interesting dimension of immune checkpoints is their candidacy for dual-checkpoint inhibition, resulting in therapeutic synergism. Furthermore, the combination of immune checkpoint inhibition with other NK cell cytotoxicity restoration strategies could also strengthen its efficacy as an antitumor therapy. Here, we have undertaken a comprehensive review of the literature to date regarding NK cell-based immune checkpoints.

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“…TIGIT has been shown to bind to CD155, a coinhibitory ligand overexpressed on multiple types of malignant tumor, where it was discovered to promote tumor progression. CD155 expression on tumor-infiltrating myeloid cells was revealed to have a negative effect on the immune antitumor response, which is conducive to immune evasion (32). Thus, CD155 expression levels on CD33 + and CD34 + cells of the BM in patients with MDS were analyzed using FCM ( Figure 4A).…”

Section: High Expression Of Tigit Limits the Function Of Nk And T Cellsmentioning

confidence: 99%

Overexpression of TIGIT in NK and T Cells Contributes to Tumor Immune Escape in Myelodysplastic Syndromes

Meng

et al. 2020

Front. Oncol.

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Targeting immune checkpoints, such as PD-1, represents a promising approach for cancer immunotherapy, achieving long-term disease remission rates in numerous types of cancer. T cell immunoglobulin and ITIM domain (TIGIT) is a checkpoint receptor associated with the antitumor roles of NK and T cells. Notably, the blockade of TIGIT has been revealed as a potential promising approach in cancer immunotherapy. However, the therapeutic potential of blocking TIGIT in myelodysplastic syndrome (MDS) remains unclear and further research is required to reveal their role. Methods: Fresh peripheral blood (PB) and bone marrow (BM) were obtained from patients with MDS and healthy donors (HDs) at the Tianjin Medical University General Hospital between January 21 2018 and March 22 2019. The present study investigated the expression levels of TIGIT on NK and T cells using flow cytometry (FCM) and PCR. In addition, other checkpoint receptors, such as CD226 and PD-1, were also investigated. To determine the mechanisms of antitumor immunity, the functions of NK and T cells expressing TIGIT were determined. Results: TIGIT was found to be highly expressed on NK and T cells of the PB, where it was involved in disease progression and the immune escape of MDS. The high expression levels of TIGIT were associated with decreased NK and T cell function, and significantly lower secretions of activation factors, such as CD107a, IFN-γ and TNF-α. Notably, blocking TIGIT enhanced the antitumor effects of NK and T cells. Conclusion: The results of the present study suggested that targeting TIGIT alone or in combination with PD-1 may be a promising anticancer therapeutic strategy in MDS.

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Targeting PVR (CD155) and its receptors in anti-tumor therapy

Cited by 126 publications

References 187 publications

Treg Heterogeneity, Function, and Homeostasis

Treg Heterogeneity, Function, and Homeostasis

NK Cell-Based Immune Checkpoint Inhibition

Overexpression of TIGIT in NK and T Cells Contributes to Tumor Immune Escape in Myelodysplastic Syndromes

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