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International Journal of Oncology Mar 2024Carcinoembryonic antigen (CEA)‑related cell adhesion molecule 6 (CEACAM6) is a cell adhesion protein of the CEA family of glycosyl phosphatidyl inositol anchored cell... (Review)
Review
Carcinoembryonic antigen (CEA)‑related cell adhesion molecule 6 (CEACAM6) is a cell adhesion protein of the CEA family of glycosyl phosphatidyl inositol anchored cell surface glycoproteins. A wealth of research has demonstrated that CEACAM6 is generally upregulated in pancreatic adenocarcinoma, breast cancer, non‑small cell lung cancer, gastric cancer, colon cancer and other cancers and promotes tumor progression, invasion and metastasis. The transcriptional expression of CEACAM6 is regulated by various factors, including the CD151/TGF‑β1/Smad3 axis, microRNA (miR)‑146, miR‑26a, miR‑29a/b/c, miR‑128, miR‑1256 and DNA methylation. In addition, the N‑glycosylation of CEACAM6 protein at Asn256 is mediated by α‑1,6‑mannosylglycoptotein 6‑β‑N‑acetylglucosaminyltransferase. In terms of downstream signaling pathways, CEACAM6 promotes tumor proliferation by increasing levels of cyclin D1 and cyclin‑dependent kinase 4 proteins. CEACAM6 can activate the ERK1/2/MAPK or SRC/focal adhesion kinase/PI3K/AKT pathways directly or through EGFR, leading to stimulation of tumor proliferation, invasion, migration, resistance to anoikis and chemotherapy, as well as angiogenesis. This article provides a review of the expression pattern, biological function and relationship with prognosis of CEACAM6 in cancer. In summary, CEACAM6 may be a valuable diagnostic biomarker and potential therapeutic target for human cancers exhibiting overexpression of CEACAM6.
Topics: Humans; Cell Adhesion; Carcinoembryonic Antigen; Adenocarcinoma; Carcinoma, Non-Small-Cell Lung; Phosphatidylinositol 3-Kinases; Pancreatic Neoplasms; Lung Neoplasms; Cell Adhesion Molecules; GPI-Linked Proteins; MicroRNAs; Cell Line, Tumor; Antigens, CD
PubMed: 38240103
DOI: 10.3892/ijo.2024.5615 -
Virulence Dec 2023Mother-to-child transmission (MTCT) is still the main route of hepatitis B virus (HBV) infection. However, the virological factors affecting HBV MTCT have not been fully...
Mother-to-child transmission (MTCT) is still the main route of hepatitis B virus (HBV) infection. However, the virological factors affecting HBV MTCT have not been fully elucidated. In this study, based on a prospective cohort of mother-infant pairs with positive maternal hepatitis B surface antigen (HBsAg), we found that the average nucleotide mutation rate of HBV preS1 promoter (SPI) region in the immunoprophylaxis success group was significantly higher than that in the immunoprophylaxis failure group. Among the nucleotide mutations of the HBV SPI region, the C2729T mutation had the highest frequency. Next, we found that the C2729T mutation promoted HBsAg release but reduced HBV production by suppressing the expression of large hepatitis B surface antigen (LHBs), and overexpressing LHBs could rescue this phenomenon. Based on the fact that the C2729T mutation could alter the binding site of hepatocyte nuclear factor 1 (HNF1) in the HBV SPI region, we uncovered that such an alteration could downregulate the transcriptional activity of SPI by attenuating the binding ability of HNF1 and HBV SPI region. This study suggests that HBV C2729T mutation may contribute to the immunoprophylaxis success of HBV MTCT by reducing HBV production, which supplements the virological factors affecting HBV MTCT.
Topics: Pregnancy; Infant; Humans; Female; Hepatitis B virus; Hepatitis B Surface Antigens; Infectious Disease Transmission, Vertical; Prospective Studies; Pregnancy Complications, Infectious; Hepatitis B e Antigens; Hepatitis B; Mutation; Nucleotides; DNA, Viral
PubMed: 36919573
DOI: 10.1080/21505594.2023.2189676 -
Aging Aug 2023The majority of oral cancer is caused by malignant transformation of squamous cells in surface of the oral mucosa. However, the relationship between CEACAM1 and oral...
OBJECTIVE
The majority of oral cancer is caused by malignant transformation of squamous cells in surface of the oral mucosa. However, the relationship between CEACAM1 and oral cancer is unclear.
METHODS
GSE23558 and GSE25099 profiles were downloaded from gene expression omnibus (GEO). Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis (WGCNA) was performed. Construction and analysis of protein-protein interaction (PPI) Network. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG), gene set enrichment analysis (GSEA), gene expression heatmap, immune infiltration analysis, comparative toxicogenomics database (CTD) were performed. TargetScan screened miRNAs that regulated central DEGs. Western blotting (WB) experiment was performed.
RESULTS
1269 DEGs were identified. According to GO analysis, they were mainly enriched in same protein binding, signal receptor binding, cell surface, epithelial cell development. KEGG analysis showed that they were mainly enriched in cancer pathways, PI3K Akt signaling pathway, TNF signaling pathway, NF kappa B signaling pathway, TGF beta signaling pathway. PPI network showed that 11 genes (CDCA8, CCNA2, MELK, KIF2C, CDC45, HMMR, TPX2, CENPF, CDK1, CEP55, CEACAM1) were obtained. Gene expression heatmap showed that CEP55 and MELK were highly expressed in oral cancer samples. CEACAM1 was lowly expressed in oral cancer samples. CEACAM1, CEP55 and MELK were involved in tumor, inflammation, necrosis, and proliferation. Western blotting (WB) showed that CEACAM1 in oral cancer samples was lower than that in normal samples, after CEACAM1 knockdown, it was lower than that in oral cancer samples.
CONCLUSION
CEACAM1 is lowly expressed in oral cancer, the lower CEACAM1, the worse prognosis.
Topics: Humans; Phosphatidylinositol 3-Kinases; Genes, cdc; Mouth Neoplasms; Cell Adhesion Molecules; Cell Cycle Proteins; Transcription Factors; Protein Serine-Threonine Kinases
PubMed: 37589542
DOI: 10.18632/aging.204960 -
IUCrJ May 2024This work focuses on molecules that are encoded by the major histocompatibility complex (MHC) and that bind self-, foreign- or tumor-derived peptides and display these... (Review)
Review
This work focuses on molecules that are encoded by the major histocompatibility complex (MHC) and that bind self-, foreign- or tumor-derived peptides and display these at the cell surface for recognition by receptors on T lymphocytes (T cell receptors, TCR) and natural killer (NK) cells. The past few decades have accumulated a vast knowledge base of the structures of MHC molecules and the complexes of MHC/TCR with specificity for many different peptides. In recent years, the structures of MHC-I molecules complexed with chaperones that assist in peptide loading have been revealed by X-ray crystallography and cryogenic electron microscopy. These structures have been further studied using mutagenesis, molecular dynamics and NMR approaches. This review summarizes the current structures and dynamic principles that govern peptide exchange as these relate to the process of antigen presentation.
Topics: Antigen Presentation; Histocompatibility Antigens Class I; Humans; Molecular Chaperones; Peptides; Receptors, Antigen, T-Cell; Crystallography, X-Ray
PubMed: 38656309
DOI: 10.1107/S2052252524002768 -
Archivum Immunologiae Et Therapiae... Aug 2023In recent years, the incidence of colorectal cancer (CRC) and breast cancer (BC) has increased worldwide and caused a higher mortality rate due to the lack of selective... (Review)
Review
In recent years, the incidence of colorectal cancer (CRC) and breast cancer (BC) has increased worldwide and caused a higher mortality rate due to the lack of selective anti-tumor therapies. Current chemotherapies and surgical interventions are significantly preferred modalities to treat CRC or BC in advanced stages but the prognosis for patients with advanced CRC and BC remains dismal. The immunotherapy technique of chimeric antigen receptor (CAR)-T cells has resulted in significant clinical outcomes when treating hematologic malignancies. The novel CAR-T therapy target antigens include GUCY2C, CLEC14A, CD26, TEM8/ANTXR1, PDPN, PTK7, PODXL, CD44, CD19, CD20, CD22, BCMA, GD2, Mesothelin, TAG-72, CEA, EGFR, B7H3, HER2, IL13Ra2, MUC1, EpCAM, PSMA, PSCA, NKG2D. The significant aim of this review is to explore the recently updated information pertinent to several novel targets of CAR-T for CRC, and BC. We vividly described the challenges of CAR-T therapies when treating CRC or BC. The immunosuppressive microenvironment of solid tumors, the shortage of tumor-specific antigens, and post-treatment side effects are the major hindrances to promoting the development of CAR-T cells. Several clinical trials related to CAR-T immunotherapy against CRC or BC have already been in progress. This review benefits academicians, clinicians, and clinical oncologists to explore more about the novel CAR-T targets and overcome the challenges during this therapy.
Topics: Humans; Female; Receptors, Chimeric Antigen; Breast Neoplasms; Immunotherapy, Adoptive; Colorectal Neoplasms; Cell- and Tissue-Based Therapy; Tumor Microenvironment; Cell Adhesion Molecules; Receptor Protein-Tyrosine Kinases; Microfilament Proteins; Receptors, Cell Surface; Receptors, Enterotoxin
PubMed: 37566162
DOI: 10.1007/s00005-023-00684-x -
Journal of Nanobiotechnology Nov 2023Aluminium adjuvants are commonly used in vaccines to stimulate the immune system, but they have limited ability to promote cellular immunity which is necessary for...
Aluminium adjuvants are commonly used in vaccines to stimulate the immune system, but they have limited ability to promote cellular immunity which is necessary for clearing viral infections like hepatitis B. Current adjuvants that do promote cellular immunity often have undesired side effects due to the immunostimulants they contain. In this study, a hybrid polymer lipid nanoparticle (HPLNP) was developed as an efficient adjuvant for the hepatitis B surface antigen (HBsAg) virus-like particle (VLP) vaccine to potentiate both humoral and cellular immunity. The HPLNP is composed of FDA approved polyethylene glycol-b-poly (L-lactic acid) (PEG-PLLA) polymer and cationic lipid 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP), and can be easily prepared by a one-step method. The cationic optimised vaccine formulation HBsAg/HPLNP (w/w = 1/600) can maximise the cell uptake of the antigen due to the electrostatic adsorption between the vaccine nanoparticle and the cell membrane of antigen-presenting cells. The HPLNP prolonged the retention of the antigen at the injection site and enhanced the lymph node drainage of antigen, resulting in a higher concentration of serum anti-HBsAg IgG compared to the HBsAg group or the HBsAg/Al group after the boost immunisation in mice. The HPLNP also promoted a strong Th1-driven immune response, as demonstrated by the significantly improved IgG2a/IgG1 ratio, increased production of IFN-γ, and activation of CD4 + and CD8 + T cells in the spleen and lymph nodes. Importantly, the HPLNP demonstrated no systemic toxicity during immunisation. The advantages of the HPLNP, including good biocompatibility, easy preparation, low cost, and its ability to enhance both humoral and cellular immune responses, suggest its suitability as an efficient adjuvant for protein-based vaccines such as HBsAg-VLP. These findings highlight the promising potential of the HPLNP as an HBV vaccine adjuvant, offering an alternative to aluminium adjuvants currently used in vaccines.
Topics: Mice; Animals; Hepatitis B Surface Antigens; Polymers; Aluminum; Hepatitis B Vaccines; Adjuvants, Immunologic; Immunity, Cellular; Nanoparticles; Immunity, Humoral
PubMed: 37993870
DOI: 10.1186/s12951-023-02116-6 -
Human Vaccines & Immunotherapeutics Dec 2023Universal infant hepatitis B vaccination has been implemented more than three decades. This study aimed to determine the prevalence of antibodies to hepatitis B surface...
Universal infant hepatitis B vaccination has been implemented more than three decades. This study aimed to determine the prevalence of antibodies to hepatitis B surface antigen (anti-HBs) and to hepatitis B core antigen (anti-HBc) in qualified blood donors in Nanjing, China. Plasmas of 815 qualified blood donors, collected from February through May 2019, were measured for anti-HBs and anti-HBc by enzyme-linked immunosorbent assay. There were 449 (55.1%) male and 366 (44.9%) female blood donors, with a median age of 28.9 years (18-60). The seroprevalence of anti-HBs was 58.8%, with no significant difference in different genders and different age groups. The overall prevalence of anti-HBc was 7.0%, with an increasing trend with age, from 0% in 18-20 years old group to 17.9% in 51-60 years old group ( = 46.7965, < .0001). The prevalence of anti-HBc in donors born after the implementation of universal hepatitis B vaccination was significantly lower than that in donors born before (1.0% vs 15.5%; = 63.6033, < .0001). Our data suggest that more than half of the blood donors in Nanjing are anti-HBs positive. Since a blood recipient usually receives more than one unit of red blood cells or plasma, passively acquired anti-HBs in blood recipients may neutralize hepatitis B virus potentially presented in blood donors with occult hepatitis B infection. In addition, the presence of anti-HBs and/or anti-HBc in blood donors may cause unique hepatitis B serological profile in blood recipients.
Topics: Infant; Humans; Male; Female; Adolescent; Young Adult; Adult; Middle Aged; Hepatitis B Surface Antigens; Blood Donors; Hepatitis B; Prevalence; Seroepidemiologic Studies; Hepatitis B virus; Hepatitis B Antibodies; Hepatitis B Core Antigens; China
PubMed: 37103976
DOI: 10.1080/21645515.2023.2206774 -
European Journal of Cell Biology Mar 2024Phagocytosis, an innate defense mechanism of multicellular animals, is initiated by specialized surface receptors. A phagocytic receptor expressed by human... (Review)
Review
Phagocytosis, an innate defense mechanism of multicellular animals, is initiated by specialized surface receptors. A phagocytic receptor expressed by human polymorphonuclear granulocytes, the major professional phagocytes in our body, is one of the fastest evolving human proteins implying a special role in human biology. This receptor, CEACAM3, is a member of the CarcinoEmbryonic Antigen-related Cell Adhesion Molecule (CEACAM) family and dedicated to the immediate recognition and rapid internalization of human-restricted pathogens. In this focused contribution, we will review the special adaptations of this protein, which co-evolves with different species of mucosa-colonizing bacteria. While the extracellular Immunoglobulin-variable (Ig)-like domain recognizes various bacterial adhesins, an Immunoreceptor Tyrosine-based Activation Motif (ITAM)-like sequence in the cytoplasmic tail of CEACAM3 constitutes the central signaling hub to trigger actin rearrangements needed for efficient phagocytosis. A major emphasis of this review will be placed on recent findings, which have revealed the multi-level control of this powerful phagocytic device. As tyrosine phosphorylation and small GTPase activity are central for CEACAM3-mediated phagocytosis, the counterregulation of CEACAM3 activity involves the receptor-type protein tyrosine phosphatase J (PTPRJ) as well as the Rac-GTP scavenging protein Cyri-B. Interference with such negative regulatory circuits has revealed that CEACAM3-mediated phagocytosis can be strongly enhanced. In principle, the knowledge gained by studying CEACAM3 can be applied to other phagocytic systems and opens the door to treatments, which boost the phagocytic capacity of professional phagocytes.
Topics: Animals; Humans; Phagocytosis; Cell Adhesion Molecules; Cytoskeleton; Signal Transduction; Phosphorylation; Carcinoembryonic Antigen
PubMed: 38215579
DOI: 10.1016/j.ejcb.2024.151384 -
British Journal of Cancer Sep 2023In many situations, the therapeutic efficacy of CAR T cells is limited due to immune suppression and poor persistence. Immunostimulatory fusion protein (IFP) constructs...
BACKGROUND
In many situations, the therapeutic efficacy of CAR T cells is limited due to immune suppression and poor persistence. Immunostimulatory fusion protein (IFP) constructs have been advanced as a tool to convert suppressive signals into stimulation and thus promote the persistence of T cells, but no universal IFP design has been established so far. We now took advantage of a PD-1-CD28 IFP as a clinically relevant structure to define key determinants of IFP activity.
METHODS
We compared different PD-1-CD28 IFP variants in a human leukemia model to assess the impact of distinctive design choices on CAR T cell performance in vitro and a xenograft mouse model.
RESULTS
We observed that IFP constructs that putatively exceed the extracellular length of PD-1 induce T-cell response without CAR target recognition, rendering them unsuitable for tumour-specific therapy. IFP variants with physiological PD-1 length ameliorated CAR T cell effector function and proliferation in response to PD-L1 tumour cells in vitro and prolonged survival in vivo. Transmembrane or extracellular CD28 domains were found to be replaceable by corresponding PD-1 domains for in vivo efficacy.
CONCLUSION
PD-1-CD28 IFP constructs must mimic the physiological interaction of PD-1 with PD-L1 to retain selectivity and mediate CAR-conditional therapeutic activity.
Topics: Humans; Mice; Animals; Immunotherapy, Adoptive; CD28 Antigens; Programmed Cell Death 1 Receptor; B7-H1 Antigen; Leukemia; Cell Line, Tumor
PubMed: 37400680
DOI: 10.1038/s41416-023-02332-9 -
Cancer Immunology Research Jul 2023Programmed death-ligand 1 (PD-L1) is a transmembrane ligand for the programmed cell death protein 1 (PD-1), a receptor that inhibits T-cell activity. The PD-L1/PD-1...
Programmed death-ligand 1 (PD-L1) is a transmembrane ligand for the programmed cell death protein 1 (PD-1), a receptor that inhibits T-cell activity. The PD-L1/PD-1 immune checkpoint axis has been successfully targeted to enhance antitumor immune responses. Tethering PD-L1 to the membrane spatially restricts its ability to inhibit immune responses, and it provides for the acute and reversible modulation of PD-L1 plasma membrane density by regulation of its trafficking. PD-L1 has functions that are independent of its role as a ligand for PD-1, and control of PD-L1 residence in different intracellular compartments might contribute to the regulation of those activities. Thus, control of PD-L1 trafficking is emerging as a key feature of its biology. Herein, we focus on current understating of PD-L1 trafficking and review current attempts to therapeutically target this process in cancer cells to enhance antitumor immunity.
Topics: B7-H1 Antigen; Programmed Cell Death 1 Receptor; Ligands
PubMed: 37290119
DOI: 10.1158/2326-6066.CIR-22-0953