B7 Family Members in Lymphoma: Promising Novel Targets for Tumor Immunotherapy?
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ABSTRACT:
SUBMITTER: Zhang W
PROVIDER: S-EPMC8044412 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Glioma, is a representative type of intracranial tumor among adults, usually has a weak prognosis and limited treatment options. Traditional therapies, including surgery, chemotherapy, and radiotherapy, have had little impact on patient survival time. Immunotherapies designed to target the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) signaling pathway have successfully treated various human cancers, informing the development of similar therapies for glioma. However, anti-PD-L1 response rates remain limited in glioma patients. Thus, exploring novel checkpoints targeting additional immunomodulatory pathways for activating durable antitumor immune responses and improving glioma outcomes is needed. Researchers have identified other B7 family checkpoint molecules, including PD-L2, B7-H2, B7-H3, B7-H4, and B7-H6. The current review article evaluates the expression of all 10 reported members of the B7 family in human glioma using The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) data, as well as summarizes studies evaluating the clinical meanings and functions of B7 family molecules in gliomas. B7 family checkpoints may contribute to different immunotherapeutic management options for glioma patients.
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Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with a five-year survival rate of approximately 5-10%. The immune checkpoint blockade represented by PD-1/PD-L1 inhibitors has been effective in a variety of solid tumors but has had little clinical response in pancreatic cancer patients. The unique suppressive immune microenvironment is the primary reason for this outcome, and it is essential to identify key targets to remodel the immune microenvironment. Some B7 family immune checkpoints, particularly PD-L1, PD-L2, B7-H3, B7-H4, VISTA and HHLA2, have been identified as playing a significant role in the control of tumor immune responses. This paper provides a comprehensive overview of the recent research progress of some members of the B7 family in pancreatic cancer, which revealed that they can be involved in tumor progression through immune-dependent and non-immune-dependent pathways, highlighting the mechanisms of their involvement in tumor immune escape and assessing the prospects of their clinical application. Targeting B7 family immune checkpoints is expected to result in novel immunotherapeutic treatments for patients with pancreatic cancer.
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Project description:The galectin family of proteins has high affinity with β-galactoside-containing glycans. These proteins participate in cell growth and differentiation, cell adhesion, cell signal transduction, cell apoptosis, and other cellular activities. In recent years, a large number of studies have described the expression and correlation of galectins in different tumors. Each member of the family plays a vital role in tumor growth, progression, angiogenesis, adhesion, and tumor immune escape. Studies on the roles of galectins in lymphoma have mainly involved galectin-1, -3, -7, and -9. The results suggest that galectins may become novel targets for precise tumor treatment. This article reviews current research progress regarding galectins in lymphoma and provides new ideas for exploring them as novel targets for treating lymphoma and other important medical issues.
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Project description:Gastric cancer (GC), with a heterogeneous nature, is the third leading cause of death worldwide. Over the past few decades, stable reductions in the incidence of GC have been observed. However, due to the poor response to common treatments and late diagnosis, this cancer is still considered one of the lethal cancers. Emerging methods such as immunotherapy with immune checkpoint inhibitors (ICIs) have transformed the landscape of treatment for GC patients. There are presently eleven known members of the B7 family as immune checkpoint molecules: B7-1 (CD80), B7-2 (CD86), B7-H1 (PD-L1, CD274), B7-DC (PDCD1LG2, PD-L2, CD273), B7-H2 (B7RP1, ICOS-L, CD275), B7-H3 (CD276), B7-H4 (B7x, B7S1, Vtcn1), B7-H5 (VISTA, Gi24, DD1α, Dies1 SISP1), B7-H6 (NCR3LG1), B7-H7 (HHLA2), and Ig-like domain-containing receptor 2 (ILDR2). Interaction of the B7 family of immune-regulatory ligands with the corresponding receptors resulted in the induction and inhibition of T cell responses by sending co-stimulatory and co-inhibitory signals, respectively. Manipulation of the signals provided by the B7 family has significant potential in the management of GC.
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Project description:Hepatitis B virus, hepatitis C virus, autoimmune hepatitis, and nonalcoholic fatty liver disease can induce chronic liver disease. The Programmed Death-1 (PD-1) inhibitory pathway assists in T cell response regulation during acute and chronic inflammation and participates in the progression of inflammatory liver disease. To examine whether PD-1 and its ligands, B7-H1 and B7-DC, are modulated during chronic necroinflammatory liver disease, we investigated expression profiles in normal patients and patients with the aforementioned conditions. Relative to liver biopsies from normal individuals, those from patients with chronic necroinflammatory liver diseases (hepatitis B virus, hepatitis C virus, and autoimmune hepatitis) contain increased numbers of PD-1-expressing lymphocytes. Kupffer cells, liver sinusoidal endothelial cells, and leukocytes express PD-1 ligands. We also detect PD-1 ligands on hepatocytes within biopsies and on isolated cells. All forms of chronic necroinflammatory liver disease examined correlate with increased B7-H1 and B7-DC expression on Kupffer cells, liver sinusoidal epithelial cells, and leukocytes. The degree of necroinflammation correlates with expression levels of PD-1 family members.These results demonstrate that expression of PD-1/PD-1 ligands links more directly with the degree of inflammation than with the underlying etiology of liver damage. The PD-1 pathway may assist the liver in protecting itself from immune-mediated destruction.
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Project description:Programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway blockade has impressively benefited cancer patients with a wide spectrum of tumors. However, its efficacy in colorectal cancer (CRC) is modest, and only a small subset of patients benefits from approved checkpoint inhibitors. Newer checkpoints that target additional immunomodulatory pathways are becoming necessary to activate durable antitumor immune responses in patients with CRC. In this review, we evaluated the mRNA expression of all 10 reported B7 family members in human CRC by retrieving and analyzing the TCGA database and reviewed the current understanding of the top three B7 family checkpoint molecules (B7-H3, VISTA, and HHLA2) with the highest mRNA expression, introducing them as putative therapeutic targets in CRC.
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Project description:Immune checkpoints (ICs) are molecules implicated in the fine-tuning of immune response via co-inhibitory or co-stimulatory signals, and serve to secure minimized host damage. Targeting ICs with various therapeutic modalities, including checkpoint inhibitors/monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), and CAR-T cells has produced remarkable results, especially in immunogenic tumors, setting a paradigm shift in cancer therapeutics through the incorporation of these IC-targeted treatments. However, the large proportion of subjects who experience primary or secondary resistance to available IC-targeted options necessitates further advancements that render immunotherapy beneficial for a larger patient pool with longer duration of response. B7-H3 (B7 Homolog 3 Protein, CD276) is a member of the B7 family of IC proteins that exerts pleiotropic immunomodulatory effects both in physiologic and pathologic contexts. Mounting evidence has demonstrated an aberrant expression of B7-H3 in various solid malignancies, including tumors less sensitive to current immunotherapeutic options, and has associated its expression with advanced disease, worse patient survival and impaired response to IC-based regimens. Anti-B7-H3 agents, including novel mAbs, bispecific antibodies, ADCs, CAR-T cells, and radioimmunotherapy agents, have exhibited encouraging antitumor activity in preclinical models and have recently entered clinical testing for several cancer types. In the present review, we concisely present the functional implications of B7-H3 and discuss the latest evidence regarding its prognostic significance and therapeutic potential in solid malignancies, with emphasis on anti-B7-H3 modalities that are currently evaluated in clinical trial settings. Better understanding of B7-H3 intricate interactions in the tumor microenvironment will expand the oncological utility of anti-B7-H3 agents and further shape their role in cancer therapeutics.
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Project description:B7x (B7-H4 or B7S1) is a member of the B7 family that can inhibit T cell function. B7x protein is absent in most normal human tissues and immune cells, but it is overexpressed in human cancers and often correlates with negative clinical outcome. The expression pattern and function of B7x suggest that it may be a potent immunosuppressive pathway in human cancers. Here, we determined the crystal structure of the human B7x immunoglobulin variable (IgV) domain at 1.59 Å resolution and mapped the epitopes recognized by monoclonal antibodies. We developed an in vivo system to screen therapeutic monoclonal antibodies against B7x and found that the clone 1H3 significantly inhibited growth of B7x-expressing tumors in vivo via multiple mechanisms. Furthermore, the surviving mice given 1H3 treatment were resistant to tumor rechallenge. Our data suggest that targeting B7x on tumors is a promising cancer immunotherapy and humanized 1H3 may be efficacious for immunotherapy of human cancers.
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Project description:The members of the B7 family, as immune checkpoint molecules, can substantially regulate immune responses. Since microRNAs (miRs) can regulate gene expression post-transcriptionally, we conducted a scoping review to summarize and discuss the regulatory cross-talk between miRs and new B7 family immune checkpoint molecules, i.e., B7-H3, B7-H4, B7-H5, butyrophilin like 2 (BTNL2), B7-H6, B7-H7, and immunoglobulin like domain containing receptor 2 (ILDR2). The current study was performed using a six-stage methodology structure and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. PubMed, Embase, Scopus, Cochrane, ProQuest, and Google Scholar were systematically searched to obtain the relevant records to 5 November 2020. Two authors independently reviewed the obtained records and extracted the desired data. After quantitative and qualitative analyses, we used bioinformatics approaches to extend our knowledge about the regulatory cross-talk between miRs and the abovementioned B7 family members. Twenty-seven articles were identified that fulfilled the inclusion criteria. Studies with different designs reported gene-miR regulatory axes in various cancer and non-cancer diseases. The regulatory cross-talk between the aforementioned B7 family molecules and miRs might provide valuable insights into the pathogenesis of various human diseases.
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Project description:B7 family members act as co-stimulatory or co-inhibitory molecules in the adaptive immune system. Thisstudy aimed to investigate the dysregulation, prognostic value and regulatory network of B7 family members in non-small cell lung cancer (NSCLC). Data for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients were extracted from public databases. Patient prognosis was determined by Kaplan-Meier analysis. The downstream signaling pathways of B7 family were identified via GO and KEGG analysis. The key B7 related genes were selected by network, correlation and functional annotation analysis. Most B7 family members were dysregulated in LUAD and LUSC. The expression of B7-1/2/H3 and B7-H5 were significantly associated with overall survival in LUAD and LUSC, respectively. The major pathway affected by B7 family was the EGFR tyrosine kinase inhibitor resistance and ErbB signaling pathway. MAPK1, MAPK3 and MAP2K1 were pivotal B7 related genes in both LUAD and LUSC. This study reveals an overall dysregulation of B7 family members in NSCLC and highlights the potential of combination use of tyrosine kinase inhibitors or MEK/ERK inhibitors with B7 member blockade for NSCLC treatment.
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