CD155: A Multi-Functional Molecule in Tumor Progression

Molfetta, Rosa; Zitti, Beatrice; Lecce, Mario; Milito, Nadia D.; Stabile, Helena; Fionda, Cinzia; Cippitelli, Marco; Gismondi, Angela; Santoni, Angela; Paolini, Rossella

doi:10.3390/ijms21030922

Cited by 67 publications

(62 citation statements)

References 88 publications

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“… 38 - 41 CD155 (PVR/necl5), a member of the nectin-like family of adhesion molecules, is widely overexpressed across most malignances and has been linked to unfavorable clinical outcomes. 17 , 42 - 45 Intriguingly, previous results reported on literature are almost similar to ours. Meanwhile, CD155 has been shown to play important tumor cell-extrinsic roles by modulating the function of tumor-infiltrating lymphocytes via interactions with both stimulatory and inhibitory receptors on T and NK cells.…”

Section: Discussionsupporting

confidence: 92%

CD155-Prognostic and Immunotherapeutic Implications Based on Multiple Analyses of Databases Across 33 Human Cancers

Zhang

Yang

et al. 2021

Technol Cancer Res Treat

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Growing evidence has suggested that CD155 participates in the regulation of many biological processes ranging cell growth, invasion, and migration from regulation of immune responses in most malignances. However, the impact of prognostic value and CD115-related immune response on the survival in multiple cancers remains incompletely clear. In our study, we assessed the prognostic significance and immune-associated mechanism of CD155 based on data from multiple databases and methods, including UCSC Xena, Oncomine, PrognoScan. We identified that CD155 was commonly upregulated in most human cancers, and High expression of CD155 was closely correlated with unfavorable clinical outcomes in 10/33 of human cancers, while CD155 at low level was responsible for better survival in KICH and PAAD. More intriguingly, CD155 expression had a significant interaction with immune function in several tumors by analyzing Tumor mutational burden and microsatellite in stability, immune score and stromal score. The correlation between immune infiltration and CD155 expression also indicated that CD155 expression positively correlated with CD4+ T cells in Head and Neck squamous cell carcinoma, Lung adenocarcinoma and Colon adenocarcinoma, while had inversely interaction with CD8+ T in Kidney renal clear cell carcinoma and Head and Neck squamous cell carcinoma as well as Tregs in Skin Cutaneous Melanoma, Head and Neck squamous cell carcinoma and Bladder Urothelial Carcinoma. These findings indicate CD155 correlates with cancer immunotherapy function. In conclusions, our observations revealed CD155 might function as immune-associated system in the development of human cancers, and acted as a promising prognostic and therapeutic target against human cancers.

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Section: Discussionsupporting

confidence: 92%

CD155-Prognostic and Immunotherapeutic Implications Based on Multiple Analyses of Databases Across 33 Human Cancers

Zhang

Yang

et al. 2021

Technol Cancer Res Treat

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Section: Introductionmentioning

confidence: 99%

“…CD155, also known as nectin-like 5 (NECL5), is a type I transmembrane glycoprotein that belongs to the immunoglobulin superfamily, and is involved in many physiological processes [ 1 – 3 ]. This protein was initially identified as a poliovirus receptor [ 4 ], and has been shown to play important roles in cell adhesion and proliferation [ 1 , 2 ]. Its overexpression has been reported to promote tumor invasion and proliferation, and is associated with poor prognosis in some types of cancer, including colorectal cancer, lung adenocarcinoma, pancreatic cancer, and hepatocellular carcinoma [ 5 – 8 ].…”

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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“…Taking in consideration these findings, we could hypothesize that PVR overexpression renders MM cells more susceptible to NK cell mediated attack at early stage of diseases, while leading to a defective NK cell activity during disease progression when receptor repertoire of these cytotoxic lymphocytes results altered and the interaction PVR/TIGIT or PVR/CD96 may play a dominant role in the BM MM microenvironment. Consistently, PVR overexpression was correlated with tumor progression and unfavorable prognosis in different cancer cell types [50][51][52].…”

Section: Discussionmentioning

confidence: 61%

Bone Marrow Stromal Cell-Derived IL-8 Upregulates PVR Expression on Multiple Myeloma Cells via NF-kB Transcription Factor

Mekhloufi

Kosta

Stabile

et al. 2020

Cancers

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Bone marrow stromal cells (BMSCs) strongly contribute to multiple myeloma (MM) progression, promoting the survival and growth of malignant plasma cells (PCs). However, the possible impact of these cells on the immune-mediated recognition of MM cells remains largely unknown. DNAM-1 activating receptor plays a prominent role in NK cell anti-MM response engaging the ligands poliovirus receptor (PVR) and nectin-2 on malignant PCs. Here, we analysed the role of MM patient-derived BMSCs in the regulation of PVR expression. We found that BMSCs enhance PVR surface expression on MM cells and promote their NK cell-mediated recognition. PVR upregulation occurs at transcriptional level and involves NF-kB transcription factor activation by BMSC-derived soluble factors. Indeed, overexpression of a dominant-negative mutant of IKBα blocked PVR upregulation. IL-8 plays a prominent role in these mechanisms since blockade of CXCR1/2 receptors as well as depletion of the cytokine via RNA interference prevents the enhancement of PVR expression by BMSC-derived conditioned medium. Interestingly, IL-8 is associated with stromal microvesicles which are also required for PVR upregulation via CXCR1/CXCR2 signaling activation. Our findings identify BMSCs as regulators of NK cell anti-MM response and contribute to define novel molecular pathways involved in the regulation of PVR expression in cancer cells.

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CD155: A Multi-Functional Molecule in Tumor Progression

Cited by 67 publications

References 88 publications

CD155-Prognostic and Immunotherapeutic Implications Based on Multiple Analyses of Databases Across 33 Human Cancers

CD155-Prognostic and Immunotherapeutic Implications Based on Multiple Analyses of Databases Across 33 Human Cancers

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

Bone Marrow Stromal Cell-Derived IL-8 Upregulates PVR Expression on Multiple Myeloma Cells via NF-kB Transcription Factor

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