CD155/PVR plays a key role in cell motility during tumor cell invasion and migration

Sloan, Kevin E.; Eustace, Brenda K.; Stewart, Jean K.; Zehetmeier, Carol; Torella, Claudia; Simeone, Marina; Roy, Jennifer E.; Unger, Christine; Louis, David N.; Ilag, Leodevico L.; Jay, Daniel G.

doi:10.1186/1471-2407-4-73

Cited by 208 publications

(225 citation statements)

References 44 publications

Supporting

Mentioning

212

Contrasting

Unclassified

Order By: Relevance

“…23 , 24 Likewise, we found high levels of TIGIT expression on CD8 + and CD4 + TILs from patient tumor samples. Moreover, the level of PD-1 expression in these samples was similarly elevated, supporting the notion of cancer immune evasion via the upregulation of inhibitory molecules.…”

Section: Discussionmentioning

confidence: 50%

“…16 In the clinical setting, prior studies have demonstrated an elevated expression of CD155 on human GBM cells and increased TIGIT expression on patient CD8 + tumor-infiltrating lymphocytes (TILs), rendering this pathway as a potential therapeutic target. 23 , 24 However, the effect of TIGIT blockade as a treatment strategy remains unknown.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM

et al. 2018

View full text Add to dashboard Cite

The use of inhibitory checkpoint blockade in the management of glioblastoma has been studied in both preclinical and clinical settings. TIGIT is a novel checkpoint inhibitor recently discovered to play a role in cancer immunity. In this study, we sought to determine the effect of anti-PD-1 and anti-TIGIT combination therapy on survival in a murine glioblastoma (GBM) model, and to elucidate the underlying immune mechanisms. Using mice with intracranial GL261-luc+ tumors, we found that TIGIT expression was upregulated on CD8+ and regulatory T cells (Tregs) in the brain compared to draining cervical lymph nodes (CLN) and spleen. We then demonstrated that treatment using anti-PD-1 and anti-TIGIT dual therapy significantly improved survival compared to control and monotherapy groups. The therapeutic effect was correlated with both increased effector T cell function and downregulation of suppressive Tregs and tumor-infiltrating dendritic cells (TIDCs). Clinically, TIGIT expression on tumor-infiltrating lymphocytes was shown to be elevated in patient GBM samples, suggesting that the TIGIT pathway may be a valuable therapeutic target. Expression of the TIGIT ligand, PVR, further portended a poor survival outcome in patients with low-grade glioma. We conclude that anti-TIGIT is an effective treatment strategy against murine GBM when used in combination with anti-PD-1, improving overall survival via modifications of both the T cell and myeloid compartments. Given evidence of PVR expression on human GBM cells, TIGIT presents as a promising immune therapeutic target in the management of these patients.

show abstract

Section: Discussionmentioning

confidence: 50%

Section: Introductionmentioning

confidence: 99%

TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM

et al. 2018

View full text Add to dashboard Cite

show abstract

“…We have previously established functional proteomic screens targeting the surface proteome of invasive cancer cells Sloan et al, 2004) to identify novel molecules required for invasion. In this study, we describe the identification of neuropilin-1, a receptor for the semaphorin family of axon guidance molecules, as pro-migratory and address its role in GBM cell migration.…”

Section: Introductionmentioning

confidence: 99%

Autocrine semaphorin 3A signaling promotes glioblastoma dispersal

et al. 2009

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is the most malignant glioma type with diffuse borders due to extensive tumor cell infiltration. Therefore, understanding the mechanism of GBM cell dispersal is critical for developing effective therapies to limit infiltration. We identified neuropilin-1 as a mediator of cancer cell invasion by a functional proteomic screen and showed its role in GBM cells. Neuropilin-1 is a receptor for semaphorin3A (Sema3A), a secreted chemorepellent that facilitates axon guidance during neural development. Although neuropilin-1 expression in GBMs was previously shown, its role as a Sema3A receptor remained elusive. Using fluorophore-assisted light inactivation and RNA interference , we showed that neuropilin-1 is required for GBM cell migration. We also showed that GBM cells secrete Sema3A endogenously, and RNA interferencemediated downregulation of Sema3A inhibits migration and alters cell morphology that is dependent on Rac1 activity. Sema3A depletion also reduces dispersal, which is recovered by supplying Sema3A exogenously. Extracellular application of Sema3A decreases cell-substrate adhesion in a neuropilin-1-dependent manner. Using immunohistochemistry, we showed that Sema3A is overexpressed in a subset of human GBMs compared with the non-neoplastic brain. Together, these findings implicate Sema3A as an autocrine signal for neuropilin-1 to promote GBM dispersal by modulating substrate adhesion and suggest that targeting Sema3A-neuropilin-1 signaling may limit GBM infiltration.

show abstract

“…18 However, unlike HSV-1, BHV-1 is unable to bind to host nectin-2, but is capable of recognizing the poliovirus receptor CD155, 18 a receptor associated with tumor cell migration and invasion. 19 One of the interesting features of BHV-1 is its strict host range compared with other herpesviruses, including HSV-1. Of particular interest is the inability of BHV-1 to productively infect human cells, 20 supported by the lack of reports of either productive BHV-1 infection or even 21 In this study, we determined the ability of BHV-1 to replicate, cause cytopathic effects and affect cellular viability in a panel of normal, immortalized and transformed human cells from a variety of histological origins.…”

Section: Introductionmentioning

confidence: 99%

Bovine herpesvirus type 1 as a novel oncolytic virus

2009

View full text Add to dashboard Cite

Oncolytic virotherapy is a promising avenue of cancer gene therapy. Current vectors include human viruses that have been engineered to replicate in tumor cells or nonhuman viruses that are naturally oncotropic and preferentially replicate in tumor cells harboring defects in innate immune pathways such as the type 1 interferon (IFN) pathway. Bovine herpesvirus type 1 (BHV-1) is a species-specific herpesvirus closely related to the human herpes simplex virus type 1 (HSV-1). Although BHV-1 does not efficiently replicate in and affect cellular viability of normal human cells, it is capable of infecting and killing various immortalized and transformed human cell types. Surprisingly, BHV-1 infection of human cells fails to elicit IFN production at the mRNA or protein level and the ability of BHV-1 to kill immortalized and transformed human cells does not correlate with defects in IFN pathways. Furthermore, although some cross-reactivity between BHV-1 and HSV-1 exists, the majority of human antibody or serum samples tested failed to neutralize BHV-1 despite possessing HSV-1 neutralizing capacity. Thus, BHV-1 is a novel candidate oncolytic virus with a distinct mechanism of tumor targeting.

show abstract

CD155/PVR plays a key role in cell motility during tumor cell invasion and migration

Abstract: Background: Invasion is an important early step of cancer metastasis that is not well understood. Developing therapeutics to limit metastasis requires the identification and validation of candidate proteins necessary for invasion and migration.

Cited by 208 publications

References 44 publications

TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM

TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM

Autocrine semaphorin 3A signaling promotes glioblastoma dispersal

Bovine herpesvirus type 1 as a novel oncolytic virus

Contact Info

Product

Resources

About