scholarly journals B7-H1 is a ubiquitous antiapoptotic receptor on cancer cells

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3635-3643 ◽  
Author(s):  
Takeshi Azuma ◽  
Sheng Yao ◽  
Gefeng Zhu ◽  
Andrew S. Flies ◽  
Sarah J. Flies ◽  
...  
Keyword(s):  
T Cell ◽  
Cancer Cells ◽  
Immune Cells ◽  
Kinase Inhibitor ◽  
Tumoricidal Activity ◽  
Immune Mediated ◽  
Programmed Death ◽  
Induce Resistance ◽  
Programmed Death 1 ◽  
Increased Susceptibility

Abstract B7-H1 is an immunoglobulin-like immune suppressive molecule broadly detectable on the majority of human and rodent cancers, and its functions have been attributed to delivering an inhibitory signal to its counter-receptor programmed death-1 (PD-1) on T cells. Here we report that B7-H1 on cancer cells receives a signal from PD-1 to rapidly induce resistance against T cell–mediated killing because crippling signaling capacity of B7-H1 but not PD-1 ablates this resistance. Importantly, loss of B7-H1 signaling is accompanied by increased susceptibility to immune-mediated tumoricidal activity. In addition to resistance against T-cell destruction, B7-H1+ cancer cells also become refractory to apoptosis induced by Fas ligation or the protein kinase inhibitor Staurosporine. Our study reveals a new mechanism by which cancer cells use a receptor on immune cells as a ligand to induce resistance to therapy.

scholarly journals Evolving Concepts: Immunity in Oncology from Targets to Treatments

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Hina Khan ◽  
Rasim Gucalp ◽  
Iuliana Shapira
Keyword(s):  
Cancer Cells ◽  
Immune Checkpoint ◽  
Suppressive Effect ◽  
Anticancer Activities ◽  
Immune Balance ◽  
Immune Mediated ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Immune Ability ◽  
Immune Checkpoint Proteins

Cancer is associated with global immune suppression of the host. Malignancy-induced immune suppressive effect can be circumvented by blocking the immune checkpoint and tip the immune balance in favor of immune stimulation and unleash cytotoxic effects on cancer cells. Human antibodies directed against immune checkpoint proteins: cytotoxic T lymphocytes antigen-4 (CTLA-4) and programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), have shown therapeutic efficacy in advanced melanoma and non-small-cell lung cancer and other malignancies. Immune check point blockade antibodies lead to diminished tolerance to self and enhanced immune ability to recognize and eliminate cancer cells. As a class these agents have immune-related adverse events due to decreased ability of effector immune cells to discriminate between self and non-self. Seventy percent of patients participating in clinical trials have experienced anticancer activities and varying degrees of immune mediated dose-limiting side effects.

scholarly journals What does PD-L1 positive or negative mean?

2016 ◽  
Vol 213 (13) ◽  
pp. 2835-2840 ◽  
Author(s):  
Antoni Ribas ◽  
Siwen Hu-Lieskovan
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cancer Cells ◽  
Cell Infiltrate ◽  
Genetic Event ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Genetic Events

Expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) is used to select patients and analyze responses to anti–PD-1/L1 antibodies. The expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence or absence. PD-L1 positivity may be a result of genetic events leading to constitutive PD-L1 expression on cancer cells or inducible PD-L1 expression on cancer cells and noncancer cells in response to a T cell infiltrate. A tumor may be PD-L1 negative because it has no T cell infiltrate, which may be reversed with an immune response. Finally, a tumor that is unable to express PD-L1 because of a genetic event will always be negative for PD-L1 on cancer cells.

scholarly journals ENHANCING THE POTENCIES OF CHIMERIC ANTIGEN RECEPTOR T CELL (CAR T CELL) BY CRISPR/CAS9 SYSTEM TO ERADICATE RETINOBLASTOMA

2020 ◽  
Vol 3 (2) ◽  
pp. 73-82
Author(s):  
Yehuda Tri Nugroho Supranoto ◽  
Muhammad Yuda Nugraha ◽  
Astuti Setyawardani
Keyword(s):  
T Cell ◽  
Cancer Cells ◽  
Chimeric Antigen Receptor ◽  
Immune Cells ◽  
Antigen Receptor ◽  
Car T Cell ◽  
Programmed Death ◽  
Car T ◽  
Engineered T Cells ◽  
Specific Antigens

Retinoblastoma (RB) is the most common primary intraocular malignancy of childhood. There is no therapies that can eradicate specifically the whole cancer cells without any side effects. The disialoganglioside 2 (GD2), one of the cancer’s cell markers that can be treated using immunotherapy, is expressed in RB. Through this fact, immunotherapy based on chimeric antigen receptor (CAR)-engineered T cells targeting cancer-specific antigens has shown great potential in treating this cancer. Although in recent studies show that immune cells are not able to destroy cancer cells because in every cancer cells there is protein programmed death ligand 1 (PD-L1). This literature review also shows the potential technology using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated protein (Cas9) method to silence PD-1 in CAR T cell, so PD-L1 can not deactivate CAR T Cell through PD-1 signaling. The combination using CAR T cell and CRISPR-Cas9 will be the great therapy to eradicate RB without any side effect.

600 In vitro anticancer and immunomodulatory activities of NBT-167, a dimer of resveratrol

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A635-A635
Author(s):  
Jeffrey Zhang ◽  
Everett Henry ◽  
L Harris Zhang ◽  
Wanying Zhang
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Immune Cells ◽  
Cell Killing ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Raw264.7 Macrophages

BackgroundResveratrol (3,4’,5-trihydroxystilbene), a stilbenoid isolated from many species of plants, is widely known for its antioxidative, anti-inflammatory, immunomodulatory and anticancer activities. Recently, novel resveratrol oligomers have been isolated from various plants; their diverse structures are characterized by the polymerization of two or more resveratrol units. Little is known regarding the anticancer and immunomodulating activities of these oligomers. In this study, we designed in vitro models to compare resveratrol side by side with its natural dimer NBT-167 for their anticancer and immunological activities.MethodsWe isolated resveratrol and its dimer (NBT-167) from plants. The potency of the compounds was compared side by side using cancer cell survival assays and immunological assays with various types of human cells including cancer cell lines, PBMCs and enriched NK, gamma delta T cells, THP-1 monocytic cells, HL-60 promyelocytic leukemia cells as well as mouse RAW264.7 macrophages.ResultsNBT-167 was found to be more potent than resveratrol in inhibiting growth of various cancer cells and modulation of cytokine production from anti-IgM, LPS, PHA or SEB stimulated PBMC. Both compounds similarly enhanced IL-2 stimulated NK and gamma delta T cell killing activity against K562 cells and modulated nitric oxide production from LPS/IFN-g induced RAW264.7 macrophages and phagocytotic activity of HL-60 cells. NBT-167 was slightly more potently than resveratrol in inhibiting chemotaxis of HL-60 cells and blocking cell cycle of THP-1 and HL-60 cells at G1/S transition. In addition, NBT-167, but not resveratrol, could increase IL-2 production and T cell proliferation stimulated with anti-CD3 and anti-CD28 and synergize with anti-PD-1 antibody to increase IL-2 and IFN-gamma production in co-culture of allotypic T cells and dendric cells (MLR).ConclusionsOur data showed that NBT-167, a dimer of resveratrol, had anticancer and immunomodulatory activities such as modulation of expression of cytokines in immune cells and induction of cancer cell-killing activities of NK and gamma delta T cells. Generally, NBT-167 appeared to have higher activities than resveratrol in modulating immune cells and inhibiting cancer cells. NBT-167 could be a promising cancer immunotherapeutic agent targeting both cancer cells and immune cells.

Critical role for programmed death 1 signaling and protein kinase B in augmented regulatory T-cell induction in cord blood

2011 ◽  
Vol 128 (6) ◽  
pp. 1369-1371 ◽  
Author(s):  
Sytze de Roock ◽  
Sanne B.E.A. Hoeks ◽  
Linda Meurs ◽  
Anouk Steur ◽  
Maarten O. Hoekstra ◽  
...  
Keyword(s):  
T Cell ◽  
Protein Kinase ◽  
Cord Blood ◽  
Regulatory T Cell ◽  
Protein Kinase B ◽  
Critical Role ◽  
Programmed Death ◽  
Cell Induction ◽  
Programmed Death 1

scholarly journals Mycoplasma bovis-Induced Inhibition of Bovine Peripheral Blood Mononuclear Cell Proliferation Is Ameliorated after Blocking the Immune-Inhibitory Programmed Death 1 Receptor

2018 ◽  
Vol 86 (3) ◽  
Author(s):  
Muhammad Suleman ◽  
Farhan S. Cyprian ◽  
Steve Jimbo ◽  
Teresia Maina ◽  
Tracy Prysliak ◽  
...  
Keyword(s):  
T Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Lung Lavage ◽  
Mycoplasma Bovis ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Programmed Death ◽  
Systemic Spread ◽  
Programmed Death 1

ABSTRACTMycoplasma bovis-induced immune suppression is a major obstacle faced by the host for controlling infections.M. bovisimpairment of antigen-specific T-cell responses is achieved through inhibiting the proliferation of peripheral blood mononuclear cells (PBMCs). This impairment may contribute to the persistence ofM. bovisinfection in various sites, including lungs, and its systemic spread to various organs such as joints, with the underlying mechanisms remaining elusive. Here, we elucidated the role of the immune-inhibitory receptor programmed death 1 (PD-1) and its ligand (PD-L1) inM. bovisinfection. Flow cytometry (FCM) analyses revealed an upregulation of PD-L1 expression on tracheal and lung epithelial cell lines afterM. bovisinfection. In addition, we found increased PD-L1 expression on purified lung lavage macrophages followingM. bovisinfection by FCM and determined its localization by immunofluorescence analysis comparing infected and control lung tissue sections. Moreover,M. bovisinfection increased the expression of the PD-1 receptor on total PBMCs and in gated CD4+and CD8+T-cell subpopulations. We demonstrated thatM. bovisinfection induced a significant decrease in CD4+PD-1INTand CD8+PD-1INTsubsets with intermediate PD-1 expression, which functioned as progenitor pools giving rise to CD4+PD-1HIGHand CD8+PD-1HIGHsubsets with high PD-1 expression levels. We blocked PD-1 receptors on PBMCs using anti-PD-1 antibody at the beginning of infection, leading to a significant restoration of the proliferation of PBMCs. Taken together, our data indicate a significant involvement of the PD-1/PD-L1 inhibitory pathway duringM. bovisinfection and its associated immune exhaustion, culminating in impaired host immune responses.

Sign in / Sign up

Export Citation Format

Share Document