Overexpression of an Immune Checkpoint (CD155) in Breast Cancer Associated with Prognostic Significance and Exhausted Tumor-Infiltrating Lymphocytes: A Cohort Study

Li, Yuchen; Zhou, Quan; Song, Qingkun; Wang, Ruibin; Lyu, Shuzhen; Guan, Xiudong; Zhao, Yanjie; Wu, Jiangping

doi:10.1155/2020/3948928

Cited by 34 publications

(41 citation statements)

References 41 publications

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“…The expression of various checkpoint proteins has been observed in BCs and particularly in TNBC, including CD155 and programmed cell death-ligand 1 (PD-L1), which recognises the programmed cell death 1 (PD-1) receptor on immune cells. 127 – 130 CRISPR/Cas9 knockout of either PD-L1 or its receptor may trigger an immune response against the tumour. 131 , 132 CRISPR knockout of CDK5 has also been shown to downregulate PD-L1 expression, inhibiting tumour growth in vitro and in vivo .…”

Section: Therapeutic Potential Of Crispr In Bcmentioning

confidence: 99%

Therapeutic applications of CRISPR/Cas9 in breast cancer and delivery potential of gold nanomaterials

Padayachee

Singh

2020

Nanobiomedicine

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Globally, approximately 1 in 4 cancers in women are diagnosed as breast cancer (BC). Despite significant advances in the diagnosis and therapy BCs, many patients develop metastases or relapses. Hence, novel therapeutic strategies are required, that can selectively and efficiently kill malignant cells. Direct targeting of the genetic and epigenetic aberrations that occur in BC development is a promising strategy to overcome the limitations of current therapies, which target the tumour phenotype. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system, composed of only an easily modifiable single guide RNA (sgRNA) sequence bound to a Cas9 nuclease, has revolutionised genome editing due to its simplicity and efficiency compared to earlier systems. CRISPR/Cas9 and its associated catalytically inactivated dCas9 variants facilitate the knockout of overexpressed genes, correction of mutations in inactivated genes, and reprogramming of the epigenetic landscape to impair BC growth. To achieve efficient genome editing in vivo, a vector is required to deliver the components to target cells. Gold nanomaterials, including gold nanoparticles and nanoclusters, display many advantageous characteristics that have facilitated their widespread use in theranostics, as delivery vehicles, and imaging and photothermal agents. This review highlights the therapeutic applications of CRISPR/Cas9 in treating BCs, and briefly describes gold nanomaterials and their potential in CRISPR/Cas9 delivery.

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Section: Therapeutic Potential Of Crispr In Bcmentioning

confidence: 99%

Therapeutic applications of CRISPR/Cas9 in breast cancer and delivery potential of gold nanomaterials

Padayachee

Singh

2020

Nanobiomedicine

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“…CD155 is a cell surface receptor which belongs to the nectin and nectin-like family of immunoglobulin-like molecules that function as the receptor for poliovirus [4]. CD155 is overexpressed on GBM [1,2] and other solid tumors, including melanoma [9], breast cancer [5], lung adenocarcinoma [6], pancreatic cancer [7], and a variety of soft tissue tumors [10]. In the context of GBM, Sloan et al were among the first to describe the overexpression of CD155 in GBM using the U87-MG malignant glioma cell line and demonstrate that it plays a role in GBM invasiveness [2].…”

Section: Expression and Function Of Cd155 In Gbmmentioning

confidence: 99%

“…Bevelacqua and colleagues measured overexpression of CD155 on melanoma cell lines WM35, A375, and M14 and samples from patients, and related such upregulation to increases in cancer cell migration and invasiveness [9]. Elsewhere, overexpression of CD155 was shown to correlate to a poorer prognostic outlook in patients with breast cancer [5], soft tissue sarcoma [10], lung adenocarcinoma, pancreatic cancer, malignant glioma, and colorectal carcinoma [2,6,7,29]. This has been largely attributed to CD155's demonstrated roles in the promotion of tumor invasion [1,2,30].…”

Section: Expression and Function Of Cd155 In Gbmmentioning

confidence: 99%

“…A cell adhesion molecule of the immunoglobulin (Ig) superfamily, CD155 is a type I transmembrane glycoprotein that was first described as a poliovirus receptor (PVR) [4]. Though its expression can be detected at low levels on epithelial and endothelial cells in a variety of tissues, its overexpression on malignant cells has been associated with poor prognosis in patients with breast cancer [5], lung adenocarcinoma [6], pancreatic cancer [7], cholangiocarcinoma [8], melanoma [9], and various soft tissue tumors [10].…”

Section: Introductionmentioning

confidence: 99%

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CD155 immunoregulation as a target for natural killer cell immunotherapy in glioblastoma

Lupo

Matosevic

2020

J Hematol Oncol

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Natural killer (NK) cells are powerful immune effectors, modulating their anti-tumor function through a balance activating and inhibitor ligands on their cell surface. Though still emerging, cancer immunotherapies utilizing NK cells are proving promising as a modality for the treatment of a number of solid tumors, including glioblastoma (GBM) and other gliomas, but are often limited due to complex immunosuppression associated with the GBM tumor microenvironment which includes overexpression of inhibitory receptors on GBM cells. CD155, or poliovirus receptor (PVR), has recently emerged as a pro-tumorigenic antigen, overexpressed on GBM and contributing to increased GBM migration and aggressiveness. CD155 has also been established as an immunomodulatory receptor, able to both activate NK cells through interactions with CD226 (DNAM-1) and CD96 and inhibit them through interaction with TIGIT. However, NK cell TIGIT expression has been shown to be upregulated in cancer, establishing CD155 as a predominantly inhibitory receptor within the context of GBM and other solid tumors, and rendering it of interest as a potential target for antigen-specific NK cell-based immunotherapy. This review will explore the function of CD155 within GBM as it relates to tumor migration and NK cell immunoregulation, as well as pre-clinical and clinical targeting of CD155/TIGIT and the potential that this pathway holds for the development of emerging NK cell-based immunotherapies.

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“…Therefore, novel targets for cancer immunotherapy are required. The expression status of CD155, an immune checkpoint protein, in patients with TNBC is not well known [ 17 – 19 ]. Additionally, the association between CD155 and PD-L1 expression in patients with TNBC has not yet been analyzed.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical analysis of CD155 expression in triple-negative breast cancer patients

et al. 2021

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Introduction CD155 is an immune checkpoint protein. Its overexpression is an indicator of poor prognosis in some types of cancer. However, the significance of CD155 expression in patients with triple-negative breast cancer, and the relationship between CD155 and programmed death-ligand 1 (PD-L1) expression, have not yet been analyzed in detail. Methods Using immunohistochemical staining and tissue microarrays, we analyzed the expression profiles of CD155 and PD-L1 in 61 patients with triple-negative breast cancer. Relapse-free survival and overall survival rates were compared according to CD155 expression. The correlation between CD155 expression and clinicopathological factors, including PD-L1 expression (using SP142 and 73–10 assays), was also examined. Results CD155 expression was noted in 25 patients (41.0%) in this cohort. CD155 expression did not correlate with pathological stage, histological grade, Ki-67 labeling index, or stromal tumor-infiltrating lymphocytes. Only PD-L1 expression in tumor cells by SP142 assay significantly correlated with CD155 expression (p = 0.035); however, PD-L1 expression in tumor cells by 73–10 assay did not show a correlation (p = 0.115). Using the 73–10 assay, 59% of patients showed CD155 and/or PD-L1 expression in tumor cells. Moreover, using the SP142 assay, 63.3% of patients showed CD155 and/or PD-L1 expression in immune cells. CD155 expression did not correlate with either relapse-free survival or overall survival (p = 0.485 and 0.843, respectively). Conclusions CD155 may be a novel target for antitumor immunotherapy. The results of this study indicate that CD155 may expand the pool of candidates with triple-negative breast cancer who could benefit from antitumor immunotherapy.

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Overexpression of an Immune Checkpoint (CD155) in Breast Cancer Associated with Prognostic Significance and Exhausted Tumor-Infiltrating Lymphocytes: A Cohort Study

Cited by 34 publications

References 41 publications

Therapeutic applications of CRISPR/Cas9 in breast cancer and delivery potential of gold nanomaterials

Therapeutic applications of CRISPR/Cas9 in breast cancer and delivery potential of gold nanomaterials

CD155 immunoregulation as a target for natural killer cell immunotherapy in glioblastoma

Immunohistochemical analysis of CD155 expression in triple-negative breast cancer patients

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