Semaphorins as Potential Immune Therapeutic Targets for Cancer

Jiang, Jun; Zhang, Fang; Wan, Yi; Fang, Ke; Yan, Zedong; Ren, Xue; Zhang, Rui

doi:10.3389/fonc.2022.793805

Cited by 11 publications

(6 citation statements)

References 106 publications

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“…The Sema7a gene is moderately expressed in the heart, lung, and pancreas in mice. Sema7a can mediate macrophage and dendritic cell migration and tumor lymphatic metastasis through integrin-b1 receptors (50). We asked whether the expression status of Sema7a and integrin-b1 protein is different between PBS-treated mice and OVA-treated mice.…”

Section: Expression Of Sema7a and Integrin-b1 In Lung Tissue Was Obvi...mentioning

confidence: 99%

Semaphorin 7a aggravates TGF-β1-induced airway EMT through the FAK/ERK1/2 signaling pathway in asthma

Peng,

Sun,

Jiang

et al. 2023

Front. Immunol.

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BackgroundTGF-β1 can induce epithelial-mesenchymal transition (EMT) in primary airway epithelial cells (AECs). Semaphorin7A (Sema7a) plays a crucial role in regulating immune responses and initiating and maintaining transforming growth factor β1 TGF-β1-induced fibrosis.ObjectiveTo determine the expression of Sema7a, in serum isolated from asthmatics and non-asthmatics, the role of Sema7a in TGF-β1 induced proliferation, migration and airway EMT in human bronchial epithelial cells (HBECs) in vitro.MethodsThe concentrations of Sema7a in serum of asthmatic patients was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of Sema7a and integrin-β1 were examined using conventional western blotting and real-time quantitative PCR (RT-PCR). Interaction between the Sema7a and Integrin-β1 was detected using the Integrin-β1 blocking antibody (GLPG0187). The changes in EMT indicators were performed by western blotting and immunofluorescence, as well as the expression levels of phosphorylated Focal-adhesion kinase (FAK) and Extracellular-signal-regulated kinase1/2 (ERK1/2) were analyzed by western blot and their mRNA expression was determined by RT-PCR.ResultsWe described the first differentially expressed protein of sema7a, in patients with diagnosed bronchial asthma were significantly higher than those of healthy persons (P<0.05). Western blotting and RT-PCR showed that Sema7a and Integrin-β1 expression were significantly increased in lung tissue from the ovalbumin (OVA)-induced asthma model. GLPG0187 inhibited TGF-β1-mediated HBECs EMT, proliferation and migration, which was associated with Focal-adhesion kinase (FAK) and Extracellular-signal-regulated kinase1/2 (ERK1/2) phosphorylation.ConclusionSema7a may play an important role in asthma airway remodeling by inducing EMT. Therefore, new therapeutic approaches for the treatment of chronic asthma, could be aided by the development of agents that target the Sema7a.

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Section: Expression Of Sema7a and Integrin-b1 In Lung Tissue Was Obvi...mentioning

confidence: 99%

Semaphorin 7a aggravates TGF-β1-induced airway EMT through the FAK/ERK1/2 signaling pathway in asthma

Peng,

Sun,

Jiang

et al. 2023

Front. Immunol.

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“…Semaphorins were initially identified as guidance cues in neural development (Kolodkin, Matthes, & Goodman, 1993; Pasterkamp & Kolodkin, 2003) but are now regarded to play crucial roles in other physiological processes including angiogenesis (Iragavarapu-Charyulu, Wojcikiewicz, & Urdaneta, 2020; Serini, Maione, Giraudo, & Bussolino, 2009), tumor microenvironment (Hui, Tam, Jiao, & Ong, 2019; Jiang et al, 2022; Nakayama, Kusumoto, Nakahara, Fujiwara, & Higashiyama, 2018; Rajabinejad et al, 2020), and immune systems (Garcia, 2019; Kanth, Gairhe, & Torabi-Parizi, 2021; M. Naito & Kumanogoh, 2023). Semaphorin 4A (Sema4A), one of the immune semaphorins, plays both pathogenic and therapeutic roles in autoimmune diseases (Cavalcanti et al, 2020; He et al, 2023), allergic diseases (Maeda et al, 2019), and cancer (Iyer & Chapoval, 2018; Liu et al, 2018; Y.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of Semaphorin 4A in keratinocytes reflects the features of non-lesional psoriasis

Kume,

Koguchi-Yoshioka,

Nakai

et al. 2024

Preprint

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Psoriasis is a multifactorial disorder mediated by IL-17-producing T cells, involving immune cells and skin-constituting cells. Semaphorin 4A (Sema4A), an immune semaphorin, is known to take part in T helper type 1/17 differentiation and activation. However, Sema4A is also crucial for maintaining peripheral tissue homeostasis and its involvement in skin remains unknown. Here, we revealed that while Sema4A expression was pronounced in psoriatic blood lymphocytes and monocytes, it was downregulated in the keratinocytes of both psoriatic lesions and non-lesions compared to controls. Imiquimod application induced more severe dermatitis in Sema4A knockout (KO) mice compared to wild-type (WT) mice. The naïve skin of Sema4AKO mice showed increased T cell infiltration and IL-17A expression along with thicker epidermis and distinct cytokeratin expression compared to WT mice, which are hallmarks of psoriatic non-lesions. Analysis of bone marrow chimeric mice suggested that Sema4A expression in keratinocytes plays a regulatory role in imiquimod-induced dermatitis. The epidermis of psoriatic non-lesion and Sema4AKO mice demonstrated mTOR complex 1 upregulation, and the application of mTOR inhibitors reversed the skewed expression of cytokeratins in Sema4AKO mice. Conclusively, Sema4A-mediated signaling cascades can be triggers for psoriasis and targets in the treatment and prevention of psoriasis.

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“…Cancer immunotherapy can easily target cell surface proteins as they are easily accessible, but finding effective targets is still challenging [14]. Literature studies indicate that Sema4A, acting as a biomarker for dendritic cell activation status and CTL stimulator, promotes the production of IFN-γ and inhibits tumour growth [15,16]. Exogenous Sema4A, on the other hand, has been shown to protect TNBC cells from hypoxia-induced cytotoxicity, inhibit cell apoptosis and promote cell proliferation [17].…”

Section: Introductionmentioning

confidence: 99%

Design of a potential Sema4A-based multi-epitope vaccine to combat triple-negative breast cancer: an immunoinformatic approach

Paranthaman

Shanthi

2023

Med Oncol

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Immunotherapy is revamping the therapeutic strategies for TNBC owing to its higher mutational burden and tumour-associated antigens. One of the most intriguing developments in cancer immunotherapy is the focus on peptide-based cancer vaccines. Thus, the current work aims to develop an efficient peptide-based vaccine against TNBC that targets Sema4A, which has recently been identified as a major regulator of TNBC progression. Initially, the antigenic peptides derived from Sema4A were determined and evaluated based on their capability to provoke immunological responses. The assessed epitopes were then linked with a suitable adjuvant (RpfB and RpfE) and appropriate linkers (AAY, GPGPG, KK and EAAAK) to preclude junctional immunogenicity. Eventually, docking and dynamics simulations are performed against TLR-2, TLR-4, TLR-7 and TLR-9 to assess the interaction between the vaccine construct and TLR receptors, as the TLR signalling pathway is critical in the host immune response. The developed vaccine was then exposed to in silico cloning and immune simulation analysis. The findings suggest that the designed vaccine could potentially evoke significant humoral and cellular immune responses in the intended organism. Considering these outcomes, the final multi-epitope vaccine could be employed to serve as an effective choice for TNBC management and may open new avenues for further studies.

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Semaphorins as Potential Immune Therapeutic Targets for Cancer

Cited by 11 publications

References 106 publications

Semaphorin 7a aggravates TGF-β1-induced airway EMT through the FAK/ERK1/2 signaling pathway in asthma

Semaphorin 7a aggravates TGF-β1-induced airway EMT through the FAK/ERK1/2 signaling pathway in asthma

Downregulation of Semaphorin 4A in keratinocytes reflects the features of non-lesional psoriasis

Design of a potential Sema4A-based multi-epitope vaccine to combat triple-negative breast cancer: an immunoinformatic approach

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