The Immunomodulatory Features of Mesenchymal Stromal Cells Derived from Wharton’s Jelly, Amniotic Membrane, and Chorionic Villi In Vitro and In Vivo Data
Ornella Parolini, Antonietta Silini in Placenta, 2016
Another costimulatory molecule that belongs to the B7 family is the B7-H3 (CD276) protein. Flow cytometry and immunohistochemical analyses have shown that it is expressed by hWJMSCs (La Rocca et al. 2013b), hAECs (Petroff and Perchellet 2010), and hCVMSCs (Abumaree et al. 2013b). In addition, the molecule has been shown to be expressed not only in naive hWJMSCs but also in their in vitro–differentiated (toward osteogenic, adipogenic, and chondrogenic lineages) counterparts, a characteristic described above also for HLA-G, -E, and -F (La Rocca et al. 2013b). B7-H3 is an important T cell–immunosuppressive molecule that has been reported to consistently downregulate human T cell cytokine production and proliferation (Leitner et al. 2009). Finally, in contrast to PD-L1, PD-L2, and B7-H3, B7-H2 (CD275 or ICOS-L), the ligand for ICOS and provider of positive costimulatory effects promoting T cell activation, differentiation, and effector responses (Coyle et al. 2000; Petroff and Perchellet 2010; Yoshinaga et al. 1999), is not expressed by hAECs (Petroff and Perchellet 2010), hAMSCs (Kronsteiner et al. 2011b), and hCVMSCs (Abumaree et al. 2013b).
Targeting Subgroup-specific Cancer Epitopes for Effective Treatment of Pediatric Medulloblastoma
Surinder K. Batra, Moorthy P. Ponnusamy in Gene Regulation and Therapeutics for Cancer, 2021
Malignant cells have the capacity to evade immunologic surveillance through the expression of unique cell surface markers making them immune resistant. One of these markers that is highly expressed in a variety of tumor types, CD47, activates the signal regulatory protein alpha (SIRPoc) on myeloid cells, which in turn, protects the malignant cells from phagocytosis by macrophages [108]. Using the anti-CD47 antibody, Hu5F9-G4, authors demonstrated not only elevated tumor cell phagocytosis and growth inhibition but also an inhibition of neuroaxis spread in xenograft models of high MYC-expressing medulloblastoma [109]. Similarly, B7-H3 (CD276), which is an immune checkpoint member of the B7 family, plays a role in the functional inhibition of T-cells and is overexpressed in a variety of solid tumors, often correlated with poor prognosis [110]. A variety of clinical-translational advances have been made in B7-H3 targeting for cancer therapy, including blocking antibodies, bispecific antibodies, small molecule inhibitors, and chimeric antigen receptor T-cell (CAR T-cell) therapy [110, 111]. In an MYC-amplified medulloblastoma xenograft model, B7-H3 CAR T-cell infusion into the posterior fossa led to dramatic reduction in tumor burden and prolonged survival [111]. Finally, an emerging and provocative new approach to high-risk medulloblastoma treatment is exploiting telomerase targeting. By incorporating a telomerase substrate, 6-thio-dG, into the telomeres of tumor cells, authors demonstrated a dose-dependent inhibition of MB cell growth in vitro with reduced tumor sphere formation and elevated apoptosis [112].
Immunotherapy
Prakash Srinivasan Timiri Shanmugam in Understanding Cancer Therapies, 2018
It is now evident that tumors co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumor antigens. Because many of the immune checkpoints are triggered by ligand-receptor interactions, they can be actively blocked by antibodies or manipulated by recombinant forms of ligands or receptors. Ipilimumab, a mAb against CTLA-4 that has acquired FDA approval for metastatic melanoma, is presently being evaluated in clinical trials along with cetuximab and intensity-modulated radiation therapy (IMRT) in individuals with advanced HNSCC (NCT01860430 and NCT01935921). A phase 1, open-label, dose escalation study of MGA271 (enoblituzumab, a humanized mAb against CD276 [B7-H3] in combination with ipilimumab in patients with B7-H3–expressing HNSCC and other solid tumors) is also proceeding (NCT02381314). Tremelimumab is another anti-CTLA4 antibody presently being assessed in clinical trials.
Proteomes of exosomes from HPV(+) or HPV(-) head and neck cancer cells: differential enrichment in immunoregulatory proteins
Published in OncoImmunology, 2019
Sonja Ludwig, Lukasz Marczak, Priyanka Sharma, Agata Abramowicz, Marta Gawin, Piotr Widlak, Theresa L. Whiteside, Monika Pietrowska
CD276 (B7-H3) is a member of the B7 co-stimulatory family with prominent expression in HNSCC28 and other tumor types.29 While its function as a T-cell co-stimulatory protein has been controversial, and it has been viewed by some as a co-inhibitory rather than co-stimulatory molecule,30 its role in modulating immune responses has been well documented.31 Strong expression of CD276 on HPV(+) tumor cells as well as HPV(+) exosomes and its relative paucity on HPV(-) tumor cells and exosomes argues for the existence of more effective immune reactivity in the former. Furthermore, calmodulin detected by MS on HPV(+) exosomes regulates calcium binding and thus immune cell activation.32 Coxsackie/adenovirus receptor (CXADR) is an adhesion molecule facilitating exosome binding to recipient cells.33 The presence of these proteins supportive of immune activities in HPV(+) cells and their exosomes fits well with the hypothesis of more robust, virus-primed anti-tumor immunity in HPV(+) malignancies.
Proteomic approaches to assist in diagnosis and prognosis of oral cancer
Published in Expert Review of Proteomics, 2021
Jamile De Oliveira Sá, Luciana Daniele Trino, Ana Karina Oliveira, Ariane Fidelis Busso Lopes, Daniela Campos Granato, Ana Gabriela Costa Normando, Erison Santana Santos, Leandro Xavier Neves, Carolina Moretto Carnielli, Adriana Franco Paes Leme
Overexpression of DPAGT1 in human OSCC tumor specimens, compared to adjacent epithelia, was associated with aberrant activation of the canonical Wnt signaling pathway that has been established as a contributor to the development and progression of many human cancers [110–112]. Moreover, using a sialylation probe to enrich glycoproteins and LC-MS/MS analysis, Chen et al. [113] identified exclusive glycoproteins in the Ca9-22 compared to SG cell line, from which B7-H3 glycoprotein was the most significant. Through MS site-specific glycoprofiling approach, the authors identified lower levels of sialylation and higher fucosylation levels in the OSCC cell line. The study also revealed that B7-H3 knockdown suppressed the tumor cell proliferation and enhanced tumor growth after B7-H3 restoration. Interestingly, in IHC analysis of 72 FFPE samples from well-differentiated OSCC patients, the glycoprotein B7-H3 is observed in higher levels and was associated with a poor prognosis. The B7-H3, also called CD276, is involved in the regulation of T-cell-mediated immune response and the regulation of non-immunological pathways, and it is a promising therapeutic target in cancer treatment [114].
B7-H3 inhibits the IFN-γ-dependent cytotoxicity of Vγ9Vδ2 T cells against colon cancer cells
Published in OncoImmunology, 2020
Huimin Lu, Tongguo Shi, Mingyuan Wang, Xiaomi Li, Yanzheng Gu, Xueguang Zhang, Guangbo Zhang, Weichang Chen
As an important member of the B7 superfamily, B7-H3 (also known as CD276) is a type I membrane protein.22 The extracellular domain of B7-H3 in mice contains one IgV domain and one IgC domain (2IgB7-H3 isoform), and two identical pairs of domains are found in human B7-H3 (4IgB7-H3 isoform).23,24 B7-H3 mRNA is broadly expressed by nonlymphoid and lymphoid organs, while the B7-H3 protein is expressed on immune cells, including dendritic cells (DCs), monocytes, natural killer (NK) cells, B cells, and T cells.25 B7-H3 was shown to modulate the biological functions of immune cells, including macrophages,22 NK cells,26 CD4+ T cells,23 and CD8+ T cells,23,27 and exerted a dual role in regulating the innate and adaptive immune responses.22 However, no reports in the literature have addressed the potential contribution of B7-H3 to the regulation of γδ T cells.
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