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 72 publications

(62 citation statements)

References 88 publications

(145 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Several cancer types showed a high level of TIGIT on the tumor-infiltrating lymphocytes (TILs) (182). TIGIT recognizes the poliovirus receptor (PVR), also known as CD155 or Necl5, as well as the Nectin-2 (CD112), or Nectin-3 ligands that are overexpressed on multiple cancer types (183)(184)(185) and linked to unfavorable prognosis in several cancers (186,187).…”

Section: Nk Cell Irsmentioning

confidence: 99%

Targeting NK Cell Inhibitory Receptors for Precision Multiple Myeloma Immunotherapy

et al. 2020

View full text Add to dashboard Cite

Innate immune surveillance of cancer involves multiple types of immune cells including the innate lymphoid cells (ILCs). Natural killer (NK) cells are considered the most active ILC subset for tumor elimination because of their ability to target infected and malignant cells without prior sensitization. NK cells are equipped with an array of activating and inhibitory receptors (IRs); hence NK cell activity is controlled by balanced signals between the activating and IRs. Multiple myeloma (MM) is a hematological malignancy that is known for its altered immune landscape. Despite improvements in therapeutic options for MM, this disease remains incurable. An emerging trend to improve clinical outcomes in MM involves harnessing the inherent ability of NK cells to kill malignant cells by recruiting NK cells and enhancing their cytotoxicity toward the malignant MM cells. Following the clinical success of blocking T cell IRs in multiple cancers, targeting NK cell IRs is drawing increasing attention. Relevant NK cell IRs that are attractive candidates for checkpoint blockades include KIRs, NKG2A, LAG-3, TIGIT, PD-1, and TIM-3 receptors. Investigating these NK cell IRs as pathogenic agents and therapeutic targets could lead to promising applications in MM therapy. This review describes the critical role of enhancing NK cell activity in MM and discusses the potential of blocking NK cell IRs as a future MM therapy.

show abstract

CD155: A Multi-Functional Molecule in Tumor Progression

Cited by 72 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

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

Targeting NK Cell Inhibitory Receptors for Precision Multiple Myeloma Immunotherapy

Contact Info

Product

Resources

About