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  • melanoma
  • Although the immune system initially responds to melanoma and mounts anti-tumor attacks, these assaults are generally ineffective, allowing more advanced melanomas to win the battle and spread beyond the primary site. (healthcanal.com)
  • In 2008, the same team, led by Markus Frank, MD , of the Transplantation Research Center of Children's and BWH, and George Murphy, MD , chief of Dermatopathology at BWH, showed in the journal Nature that a key reason for melanoma virulence is a small group of tumor stem cells that are able to grow despite chemotherapy drugs, allowing the tumor to re-grow and progress. (healthcanal.com)
  • These molecules work, they found, by triggering white blood cells known as regulatory T cells (T-regs), to dampen the normal anti-melanoma response. (healthcanal.com)
  • Melanoma stem cell targeting holds promise for an absolute cure, because you're hitting the cells that really matter - the cells that drive tumor progression," says Murphy. (healthcanal.com)
  • For example, inhibition of PD-1 and B7.2 on melanoma stem cells could render them vulnerable not only to immune defenses, but also to treatments that are currently only effective against the more susceptible non-stem cell component of the tumor. (healthcanal.com)
  • Specifically, they hope to participate in several ongoing or future clinical trials that target specific immunologic signaling pathways in melanoma patients (using anti-PD-1 antibodies, for example), to track the response of ABCB5-positive melanoma stem cells. (healthcanal.com)
  • Here, we use a novel anti-CD47 single domain antibody, derived from an alpaca, in an immunocompetent mouse model of melanoma and find that, in contrast to immunodeficient models, CD47 blockade alone is insufficient to enhance the effects of antimelanoma antibodies. (pnas.org)
  • D ) Melanoma tumor volumes at various times after s.c. injection of 4 × 10 4 C3d + B16 ( n = 10), or 4 × 10 4 C3d - ( n = 9) melanoma cells in syngeneic mice. (jci.org)
  • A group at the National Cancer Institute demonstrated remarkable efficacy by infusing melanoma-specific T cells (obtained by growing tumor-infiltrating T cells ex vivo) into melanoma patients treated with lymphodepleting chemotherapy. (wikipedia.org)
  • These findings compare favorably with standard-of-care therapies for melanoma which generally lead to tumor regressions in only ~10-12% of patients. (wikipedia.org)
  • Interim results from a phase III trial of talimogene laherparepvec in melanoma showed a significant tumour response compared to administration of GM-CSF alone. (wikipedia.org)
  • In 1985 IL-2 administration produced durable tumor regressions in some patients with metastatic melanoma. (wikipedia.org)
  • In 1988 autologous TILs were shown to reduce metastatic melanoma tumors. (wikipedia.org)
  • PD-L1 is expressed on almost all murine tumor cell lines, including PA1 myeloma, P815 mastocytoma, and B16 melanoma upon treatment with IFN-γ. (wikipedia.org)
  • antigen
  • Although carcinoembryonic antigen (CEA)-related cell adhesion molecule 1 (CEACAM1) has been viewed as a tumor suppressor, increasing clinical evidence shows that high levels of CEACAM1 expression on tumors correlates with poor prognosis and high risk of metastasis. (pubmedcentralcanada.ca)
  • While a host's homologous recombination can act as a defense mechanisms for fixing DNA double stranded breaks (DSBs), it can also create changes in antigenic DNA that can create new, unrecognizable proteins that allow the antigen to escape recognition by the host's immune response. (wikipedia.org)
  • Cancer vaccines seek to target a tumor-specific antigen and distinct from self-proteins. (wikipedia.org)
  • mice
  • The in vivo development of MHC-I-deficient tumors is much favored in PKC θ −/− mice compared with wild-type mice. (frontiersin.org)
  • Here, we show that CD47 blockade alone or in combination with a tumor-specific antibody fails to generate antitumor immunity against syngeneic B16F10 tumors in mice. (pnas.org)
  • In light of the recent data that enzymes mediating MDSC-dependent immunosuppression in mice are active also in humans, these findings demonstrate a potentially novel use of PDE5 inhibitors as adjuncts to tumor-specific immune therapy. (rupress.org)
  • It has been noted that tumors that persist in the equilibrium phase show reduced immunogenicity when compared to tumors which have been grown in immunodeficient mice (Shankaran et al. (wikipedia.org)
  • High doses of IL-2 could inhibit tumor growth in mice. (wikipedia.org)
  • A virus that has been shown to cause breast cancer in mice is mouse mammary tumor virus. (wikipedia.org)
  • In this paper, Stutman tested whether athymic, nude mice which lack an adaptive immune system have an increased incidence of tumors. (wikipedia.org)
  • His finding that the incidence of tumor formation was the same in nude mice, as compared to wild type mice, led to the strong belief, for over 20 years, that the immune system played no role in preventing the initiation or the prevention of tumors. (wikipedia.org)
  • With the explosion of new information about the role of the innate immune system over the last two decades, and with the knowledge that the innate immune system was intact in the nude mice that Stutman had used, Schreiber repeated these experiments using a strain of mice he bred to lack both innate and adaptive immunity. (wikipedia.org)
  • Dr. Schreiber's lab was the first to generate STAT1 deficient mice and has worked to characterize the important role of this gene in innate immunity. (wikipedia.org)
  • In mice, expression of this gene is induced in the thymus when anti-CD3 antibodies are injected and large numbers of thymocytes undergo apoptosis. (wikipedia.org)
  • immunogenic
  • It has long been a matter of debate whether tumors are spontaneously immunogenic in patients. (aacrjournals.org)
  • Melanomas are highly immunogenic cancers, initially provoking anti-tumor attacks, as evidenced by patients whose brown-black skin tumors seem to have partly dissolved away, producing regions of pink to white coloration where pigment previously existed. (healthcanal.com)
  • Despite expression of immunogenic polypeptides, tumors escape immune surveillance by engaging T cell checkpoint regulators and expanding Tregs, among other mechanisms. (jci.org)
  • pathogens
  • The most common of antigenic escape mechanisms, homologous recombination, can be seen in a wide variety of bacterial pathogens, including Helicobacter pylori, a bacterium that infects the human stomach. (wikipedia.org)
  • This process is important in building immunity, and many pathogens have evolved methods to evade attacks by phagocytes. (wikipedia.org)
  • therapeutic
  • However, reovirus-mediated antitumor immunologic events during and after oncotherapy as well as their specific therapeutic capabilities have not been thoroughly explored. (aacrjournals.org)
  • immunosurveillance
  • Cancer immunosurveillance and immunoediting are based on protection against development of tumors in animal systems and (ii) identification of targets for immune recognition of human cancer. (wikipedia.org)
  • clinically
  • The degree of diversity correlated with clinically relevant breast tumor subtypes and in some tumors was markedly different between the in situ and invasive cell populations. (blogspot.com)
  • In summary, in this study we have demonstrated the power of analyzing tumors as ecosystems and suggest that quantitative measures of intratumor diversity might be clinically useful biomarkers predicting prognosis and response to treatment. (blogspot.com)
  • Our preliminary studies demonstrate that HER-2 specific humoral immunity occurs commonly in Trastuzumab-treated patients and that the appearance of HER-2 humoral immunity occurs more commonly in clinically responding patients. (dana.org)
  • cell-mediated
  • NKG2D plays a pivotal role in NK cell- and T cell-mediated immunity against cancers and infections, as well as in the development of autoimmune diseases ( Lanier, 2008 ). (pubmedcentralcanada.ca)
  • T-cell mediated immunity, by contrast, has the potential to recognize targets expressed either extra- or intra-cellularly and has therefore been studied extensively for treatment of these diseases. (wikipedia.org)
  • elimination
  • The elimination, functional inhibition, or differentiation of MDSCs in tumor-bearing hosts can restore CD8 + T cell responsiveness ( 10 , 11 ), thereby implicating their role in tumor-induced immunosuppression. (rupress.org)
  • It is made up of three phases: elimination, equilibrium, and escape. (wikipedia.org)
  • The elimination phase consists of the following four phases: The first phase involves the initiation of an antitumor immune response. (wikipedia.org)
  • Tumor cell variants which have acquired resistance to elimination then enter the escape phase. (wikipedia.org)
  • It has three main phases: elimination, equilibrium and escape. (wikipedia.org)
  • metastatic
  • Reovirus efficiently destroys local as well as distant metastatic tumors in immunocompromised animals even after a single injection administered through intravenous, intraperitoneal, or intratumoral routes ( 25 - 28 ). (aacrjournals.org)
  • ligand
  • Durable tumor immunity required programmed death-ligand 1 (PD-L1) blockade in combination with an antitumor antibody, with incorporation of CD47 antagonism substantially improving response rates. (pnas.org)
  • Similarly, the programmed death-ligand (PD-L 1,2) interferes with the antitumor function of CTLs by binding with PD-1 receptor. (nutriforce.cn)
  • blockade
  • However, recent reports show that synchronized blockade or overriding of tumor immune evasion strategies with appropriate immunomodulatory intervention may overcome immunologic tolerance and promote tumor regression ( 1 , 17 , 18 ). (aacrjournals.org)
  • In our mouse models, we show that pharmacologic PDE5 blockade down-regulates MDSC suppressive pathways and restores antitumor immunity. (rupress.org)
  • cancer
  • These findings should advance our current knowledge in devising antitumor immunotherapeutic remedies to complement virotherapy-mediated tumor destruction and restrict cancer remission in clinical settings. (aacrjournals.org)
  • In several tumors, stem cell-like and more-differentiated cancer cell populations were genetically distinct, leading us to question the validity of a simple differentiation hierarchy-based cancer stem cell model. (blogspot.com)
  • Such cellular milieu further boosts immune tolerance and eventually appoint immunity for cancer advantage. (cnrs-orleans.fr)
  • Some of those miRs were found to efficiently regulate cancer immunity and their dysregulation efficiently programs aberrant angiogenesis and cancer metastasis. (cnrs-orleans.fr)
  • Does Anti-Tumor Antibody Treatment Improve Immune Responses and Outcomes of Breast Cancer? (dana.org)
  • Anti-tumor antibody treatments have improved clinical outcomes for breast cancer and lymphoma patients. (dana.org)
  • Researchers have thought that the monoclonal antibody breast cancer treatment Trastuzumab works by interfering with processes that regulate tumor growth. (dana.org)
  • The laboratory conducts research on cancer vaccines focuses on augmenting CD4 "helper" T cell immunity using peptide epitopes. (dana.org)
  • Dr. Restifo's most recent efforts include a focus on how elements - literally from the periodic table - influence cancer immunity. (wikipedia.org)
  • It is from discoveries such as this and the role of HPV in cervical cancer development that research is currently being undertaken to discover whether or not human mammary tumour virus is a cause of breast cancer in humans. (wikipedia.org)
  • Subsequent work showed that tumors escape immune recognition by losing their antigenicity in a process he named cancer immunoediting. (wikipedia.org)
  • A new class of drugs that block PD-1, the PD-1 inhibitors, activate the immune system to attack tumors and are therefore used with varying success to treat some types of cancer. (wikipedia.org)
  • cellular
  • The varied cellular responses to RA treatment may provide an explanation for the failure of RA to reach its full potential in treatment and prevention of solid tumors, including breast, lung, ovarian, prostate, and pancreatic cancers. (omicsonline.org)
  • Our analyses showed a high degree of genetic heterogeneity both within and between distinct tumor cell populations that were defined based on markers of cellular phenotypes including stem cell-like characteristics. (blogspot.com)
  • evidence
  • There is currently little evidence to support the existence of an equilibrium phase, aside from the observation that cancers have been shown to lie dormant, i.e. to go into remission, in a person's body for years before re-emerging again in the final escape phase. (wikipedia.org)
  • regressions
  • In a series of studies (to 2005) of this approach, up to 70% of treated patients were shown to have regressions of their tumors, many of which had been considerable in size and refractory to other therapies. (wikipedia.org)
  • antibody
  • The American biotech company Celldex Therapeutics is working on CDX-1127, an agonistic anti-CD27 monoclonal antibody which in animal models has been shown to be effective in the context of T cell receptor stimulation. (wikipedia.org)
  • A now-defunct Seattle-based biotechnology company called VLST in-licensed an anti-CD40 agonist monoclonal antibody from Pfizer in 2012. (wikipedia.org)
  • An example is BMS-986016, an anti-LAG3 monoclonal antibody that is currently in phase 1 clinical testing. (wikipedia.org)
  • responses
  • These TAAs have facilitated the analysis of T cell responses to tumors and are promising targets for immunotherapeutic strategies. (aacrjournals.org)
  • However, recent findings suggest that combination of reovirus-mediated oncolysis and host immune responses is necessary to achieve efficient tumor regression associated with this virotherapy ( 29 ). (aacrjournals.org)
  • Many head and neck cancers are able to escape immune responses in a variety of ways. (wikipedia.org)
  • We will further address whether this association is causal rather than being merely a marker of tumor responses, by determining whether patients with favorable high affinity FcgR polymorphs are more likely develop both clinical and immunological responsiveness. (dana.org)
  • clinical
  • In fact the Hopkins published preliminary results of a clinical study testing the basic immunotransplant concept in acute myeloid leukemia demonstrating encouraging signals of enhanced anti-tumor immunity. (wikipedia.org)
  • Therapeutics
  • Startups including Juno Therapeutics exploit the combination of aggressive tumors and FDA willingness to approve potential therapies for such ailments to accelerate approvals for new therapies. (wikipedia.org)
  • mutations
  • During this period of Darwinian selection, new tumor cell variants emerge with various mutations that further increase overall resistance to immune attack. (wikipedia.org)
  • induces
  • In the second phase, newly synthesized IFN-gamma induces tumor death (to a limited amount) as well as promoting the production of chemokines CXCL10, CXCL9 and CXCL11. (wikipedia.org)
  • dysregulation
  • Taken together, data from recent reports imply that dysregulation of tumor glycolysis could facilitate induction of immune sensitive surface ligands leading to increased efficacy of antitumor immunotherapeutics. (nutriforce.cn)
  • anticancer
  • Thus, the achievement of optimum anticancer effects during oncotherapy hinges on a harmonious exploitation of reovirus-mediated direct oncolysis and antitumor immune activities. (aacrjournals.org)
  • In this mini-review, targeting tumor glycolysis has been discussed to evaluate its potential implications to enhance and/or facilitate anticancer immunity. (nutriforce.cn)
  • Blood vessel normalization strategies that equilibrate oxygen levels within tumor and fix abnormal vasculature bring exciting promises to future anticancer therapies especially when combined with conventional chemotherapy. (cnrs-orleans.fr)