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17 papers found.
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Is CD47 an innate immune checkpoint for tumor evasion?

Cluster of differentiation 47 (CD47) (also known as integrin-associated protein) is a ubiquitously expressed glycoprotein of the immunoglobulin superfamily that plays a critical role in self-recognition. Various solid and hematologic cancers exploit CD47 expression in order to evade immunological eradication, and its overexpression is clinically correlated with poor prognoses. One ...

Mapping the Interactome of a Major Mammalian Endoplasmic Reticulum Heat Shock Protein 90

Up to 10% of cytosolic proteins are dependent on the mammalian heat shock protein 90 (HSP90) for folding. However, the interactors of its endoplasmic reticulum (ER) paralogue (gp96, Grp94 and HSP90b1) has not been systematically identified. By combining genetic and biochemical approaches, we have comprehensively mapped the interactome of gp96 in macrophages and B cells. A total of ...

Exploring the Functional Complementation between Grp94 and Hsp90

Grp94 and Hsp90 are the ER and cytoplasmic paralog members, respectively, of the hsp90 family of molecular chaperones. The structural and biochemical differences between Hsp90 and Grp94 that allow each paralog to efficiently chaperone its particular set of clients are poorly understood. The two paralogs exhibit a high degree of sequence similarity, yet also display significant ...

Interaction of Toll-Like Receptors with the Molecular Chaperone Gp96 Is Essential for Its Activation of Cytotoxic T Lymphocyte Response

The heat shock protein gp96 elicits specific T cell responses to its chaperoned peptides against cancer and infectious diseases in both rodent models and clinical trials. Although gp96-induced innate immunity, via a subset of Toll like receptors (TLRs), and adaptive immunity, through antigen presentation, are both believed to be important for priming potent T cell responses, direct ...

Pass quantity, focus on quality

Journal of Hematology & Oncology is pleased to see the exponential growth in the number of publications from China, especially in hematology and oncology. This editorial calls for putting more weight on the quality of the future scientific output and invites rigorous dialogs among policy makers, granting agencies, academic leaders, physicians, and scientists, followed by concrete ...

Sex Differences in Monocyte Activation in Systemic Lupus Erythematosus (SLE)

Introduction TLR7/8 and TLR9 signaling pathways have been extensively studied in systemic lupus erythematosus (SLE) as possible mediators of disease. Monocytes are a major source of pro-inflammatory cytokines and are understudied in SLE. In the current project, we investigated sex differences in monocyte activation and its implications in SLE disease pathogenesis. Methods Human ...

Fact or fiction - identifying the elusive multiple myeloma stem cell

Multiple Myeloma (MM) is a debilitating disease of proliferating and malignant plasma cells that is currently incurable. The ability of monoclonal recurrence of disease suggests it might arise from a stem cell-like population capable of self-renewal. The difficulty to isolate the cancer stem-like cell in MM has introduced confusion toward this hypothesis. However, recent evidence ...

Lower circulating platelet counts and antiplatelet therapy independently predict better outcomes in patients with head and neck squamous cell carcinoma

Background Head and neck squamous cell carcinoma (HNSCC) mortality rates have not shown significant reduction in decades. Platelets are being implicated in having cancer-promoting roles, an observation supported by the adverse outcomes associated with thrombocytosis in many malignancies associated with thrombocytosis. However, the prognostic significance of platelet counts in HNSCC ...

Murine but Not Human Basophil Undergoes Cell-Specific Proteolysis of a Major Endoplasmic Reticulum Chaperone

Introduction Basophil has been implicated in anti-parasite defense, allergy and in polarizing TH2 response. Mouse model has been commonly used to study basophil function although the difference between human and mouse basophils is underappreciated. As an essential chaperone for multiple Toll-like receptors and integrins in the endoplasmic reticulum, gp96 also participates in ...

Unfolded protein response in cancer: the Physician's perspective

The unfolded protein response (UPR) is a cascade of intracellular stress signaling events in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER). Cancer cells are often exposed to hypoxia, nutrient starvation, oxidative stress and other metabolic dysregulation that cause ER stress and activation of the UPR. Depending on the ...

Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker

Background Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern ...

Heat-shock proteins in infection-mediated inflammation-induced tumorigenesis

Inflammation is a necessary albeit insufficient component of tumorigenesis in some cancers. Infectious agents directly implicated in tumorigenesis have been shown to induce inflammation. This process involves both the innate and adaptive components of the immune system which contribute to tumor angiogenesis, tumor tolerance and metastatic properties of neoplasms. Recently, ...

The anti-myeloma activity of a novel purine scaffold HSP90 inhibitor PU-H71 is via inhibition of both HSP90A and HSP90B1

Chiosis 2 Zihai Li 1 0 Myeloma Institute for Research & Therapy, University of Arkansas for Medical Sciences , Little Rock, AR , USA 1 Department of Immunobiology & Cancer Immunology, Hollings Cancer

Oocyte–Targeted Deletion Reveals That Hsp90b1 Is Needed for the Completion of First Mitosis in Mouse Zygotes

Background Hsp90b1 is an endoplasmic reticulum (ER) chaperone (also named Grp94, ERp99, gp96,Targ2, Tra-1, Tra1, Hspc4) (MGI:98817) contributing with Hspa5 (also named Grp78, BIP) (MGI:95835) to protein folding in ER compartment. Besides its high protein expression in mouse oocytes, little is known about Hsp90b1 during the transition from oocyte-to-embryo. Because the constitutive ...

Ovarian cancer immunotherapy: opportunities, progresses and challenges

Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against ...

Identification of gp96 as a Novel Target for Treatment of Autoimmune Disease in Mice

Heat shock proteins have been implicated as endogenous activators for dendritic cells (DCs). Chronic expression of heat shock protein gp96 on cell surfaces induces significant DC activations and systemic lupus erythematosus (SLE)-like phenotypes in mice. However, its potential as a therapeutic target against SLE remains to be evaluated. In this work, we conducted chemical approach ...