• The primary types of cellular adoptive immunotherapies are T cell therapies. (wikipedia.org)
  • Other therapies include CAR-T therapy, CAR-NK therapy, macrophage-based immunotherapy and dendritic cell therapy. (wikipedia.org)
  • Although immunotherapy with immune checkpoint blockade and targeted therapy was used to treat and improve the survival of patients with several types of cancers, such as non-small cell lung cancer, many patients still develop disease progression even after receiving these therapies. (wikipedia.org)
  • Current cellular adoptive therapies consist of the ex-vivo expansion of TILs from resected tumors and transferred back to the patients' bodies with support of interleukin -2 (IL-2). (wikipedia.org)
  • In current clinical development, targeting CD19 + B cell malignancies, which include acute and chronic B-cell leukaemia and B-cell non-Hodgkin lymphomas (NHLs), with anti-CD19 CAR-T cells is one of the most advanced adoptive T-cell therapies and has been approved by the FDA. (nature.com)
  • Despite their efficiency, adoptive T-cell therapies show unique toxicities, which are distinct from those seen with conventional chemotherapies, monoclonal antibodies (mAbs), and small-molecule-targeted therapies. (nature.com)
  • In just a few years, CAR T-cell and other adoptive T-cell therapies have emerged as among the most promising forms of cancer immunotherapy. (medicalxpress.com)
  • The findings, based on 15 years of painstaking work to recreate and assemble key components of the signal-processing mechanism, may help researchers fine-tune T-cell therapies to the requirements of individual patients, the study authors say. (medicalxpress.com)
  • It unlocks novel dimensions by uncovering elusive cell populations and tumor heterogeneities for early detection, unraveling mechanisms of treatment resistance, tailoring therapies to individuals, and illuminating metastasis and cachexia pathways, thereby opening fresh avenues for preventive strategies. (frontiersin.org)
  • Cancer immunotherapies can be divided into four major categories: - Cytokines/immunomodulation agents - Monoclonal antibodies - Cell‑based therapies - Oncolytic viruses Though monoclonal antibodies currently represent the largest class of commercialized cancer immunotherapies, cell‑based therapies are rapidly making headway. (technologynetworks.com)
  • Unfortunately, many patients still progress and acquire resistance to immunotherapy and molecularly targeted therapies. (biomedcentral.com)
  • Thus, we have defined a mechanism of NK cell-mediated control of metastases in vivo that may help develop NK cell-dependent cancer therapies. (bioxcell.com)
  • Adoptive therapies with genetically modified somatic T cells rendered HIV resistance have shown promise for AIDS therapy. (wisc.edu)
  • Recently, the lab of Dr. P. Agostinis documented that immunogenic cell death mediated by ER stress can be harnessed to develop novel and clinically relevant, next-generation dendritic cell-based immunotherapies for brain tumors. (euroacadti.eu)
  • Tumor immunotherapy brings substantial and long-term clinical benefits that can even cure tumors. (hindawi.com)
  • Tumor immunotherapy refers to novel therapeutic measures that turn the immune system into a destructive force against tumors [ 1 ]. (hindawi.com)
  • Adoptive cellular therapy, especially chimeric antigen receptor (CAR) T cell therapy, has gained unprecedented success among hematologic tumors [ 11 ]. (hindawi.com)
  • This therapy has shown to be more effective in treating solid tumors than other cellular adoptive immunotherapies such as CAR T cell therapy. (wikipedia.org)
  • However, as tumors progress, cancerous cells develop immunosuppressive mechanisms that circumvent NK cell-mediated killing, allowing for tumor escape and proliferation. (frontiersin.org)
  • However, the mechanisms by which NK cells control tumors in vivo are unclear. (bioxcell.com)
  • Immunotherapy is currently considered as a promising next-generation therapeutic strategy for various cancers thanks to its ability to modulate cell-specific immune responses toward tumors [ 1 ], which has gradually remodeled the landscape of clinical anticancer modality [ 2 ]. (thno.org)
  • Optimization of the design of CAR vectors, exploration of new targets, addition of safe switches and combination with other treatments bring new vitality to the CAR-T cell based immunotherapy against solid tumors. (ijbs.com)
  • It may be achieved, at least partially, by more extensive basic studies investigating the spatiotemporal dynamics of T cell activation by CARs and unraveling the connection between T cell migration in solid tumors and the effectiveness in eradication of solid tumors and metastases [ 5 ]. (ijbs.com)
  • However, it also points out the weaknesses of immunotherapy, as not all tumors respond to therapy and the co-administration of different immunomodulators may be severely limited due to their systemic toxicity. (mdpi.com)
  • Chimeric antigen receptor T-cells (CAR-T) are predominantly used in cancer immunotherapy. (wikipedia.org)
  • IL-2 and IFN-γ), immune checkpoint blockade (ICB) therapy (e.g., anti-PD-1/PD-L1 antibodies), and adoptive T-cell transfer (e.g., chimeric antigen receptor (CAR) T-cell therapy) [ 3 - 5 ]. (thno.org)
  • Other TCR immunotherapies use genetically engineered T cells employing natural TCRs rather than chimeric receptors to target specific tumor cell antigens, also called neoantigens. (medicalxpress.com)
  • Cytokines, cancer vaccines, adoptive cell transfers, and especially checkpoint inhibitors constitute valuable elements in the immunotherapeutic armamentarium. (frontiersin.org)
  • Moreover, TAMs usually display M2-like phenotypes that exert tumor-promoting role in TME, and promote production of related immunosuppressive factors that trigger immunotherapy resistance, including cytokines, chemokines, growth factors and soluble signaling mediators [ 12 ]. (thno.org)
  • Kupffer cells, hepatic stellate cells and sinusoidal endothelium) and infiltrating leukocytes (e.g., monocytes, monocyte-derived macrophages, neutrophils and lymphocytes). (mdpi.com)
  • Additionally, the hexon component of AdV capsid can bind to coagulation factor X (FX) to activate TLR4 on the surface of splenic macrophages and thereby stimulate NF-κB dependent activation of IL-1β, which may help recruit polymorphonuclear leukocytes to the marginal zone of the spleen and clear virus from the spleen rapidly [49, 50]. (genemedi.com)
  • IFNγ exerts immunoregulatory, anti-proliferative, anti-viral, and proinflammatory activities and plays an important role in activation, growth, and differentiation of T and B lymphocytes, macrophages, NK cells and other non-hematopoietic cell types. (bioxcell.com)
  • Wei X, Wang J, Liang M, Song M. Development of functional nanomedicines for tumor associated macrophages-focused cancer immunotherapy. (thno.org)
  • Clinical cancer immunotherapies are usually impeded by tumor immunosuppression driven by tumor associated macrophages (TAMs). (thno.org)
  • Immune checkpoint inhibitors (ICIs) are antibodies that target crucial signaling pathways, such as programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), to improve the activation of T cells and enhance the immune response to cancer cells. (hindawi.com)
  • Activated γδ T cells exhibit strong cytotoxic activity and cytokine secretion functions and are effective antitumor lymphocytes with simple and direct recognition modes and rapid responses. (explorationpub.com)
  • Outcomes for patients with melanoma have improved over the past decade with the clinical development and approval of immunotherapies targeting immune checkpoint receptors such as programmed death-1 (PD-1), programmed death ligand 1 (PD-L1) or cytotoxic T lymphocyte antigen-4 (CTLA-4). (biomedcentral.com)
  • Most of them generally follow the same pathway to make immune-activated cytotoxic T lymphocytes (CTLs) abundantly infiltrate into tumor tissues and destroy tumor cells [ 6 ]. (thno.org)
  • Melanoma was the first type of tumor that provided insight into cancer immunotherapy due to its high immunogenicity. (wikipedia.org)
  • This included sessions dedicated to systems biology on immunotherapy, immunogenicity and gene expression profiling, biomarkers, and combination treatment strategies. (biomedcentral.com)
  • Nevertheless, there is an established way through which to increase the immunogenicity of immunotherapy-by the use of adjuvants. (mdpi.com)
  • 2) Achieving full function of T cells and tumor microenvironment (TME) with different immunosuppressive mechanisms is another primary concern. (wikipedia.org)
  • Moreover, CAR-T cells are vulnerable to immunosuppressive mechanisms. (nature.com)
  • However, increasing data has indicated that the clinical potential of most immunotherapies is usually hampered by immunosuppressive status of the tumor microenvironment (TME) [ 7 ]. (thno.org)
  • Among most immunosuppressive cells, TAMs, as crucial drivers of immunosuppressive TME, account for the largest proportion of immune cells in the TME (approximately 50% of tumor mass) [ 9 , 10 ], which possess highly heterogeneity and play a complex regulatory role in tumor immunity and immunotherapy due to helping tumor evade immune surveillance [ 11 ]. (thno.org)
  • TIL therapy isolates tumor-infiltrating lymphocytes (TILs), which are naturally occurring T cells in cancer patients that have already recognised cancer cells and infiltrated into the tumor as an anti-tumor response from their own immune system after tumor resection. (wikipedia.org)
  • Breakthroughs in anti-tumor immunity have led to unprecedented advances in immunotherapy, yet it is now clear that the tumor microenvironment (TME) restrains immunity. (elifesciences.org)
  • Therapeutic approaches that take advantage of the anti-tumor activities of NK cells, such as the adoptive transfer of genetically modified NK cells and the modulation of checkpoint molecules, turned out to be promising immunotherapeutic strategies to eliminate cancer. (encyclopedia.pub)
  • Alternative inhibitory receptors have been identified that may be targeted for anti-tumor immune therapy, such as lymphocyte-activation gene-3 (LAG-3), as have several potential target oncogenes for molecularly targeted therapy, such as tyrosine kinase inhibitors. (biomedcentral.com)
  • instead of targeting tumor cells, the goal of immunotherapy is to augment and expand the immune system's intrinsic antitumor response. (frontiersin.org)
  • First described in 1975, NK cells were initially identified as a distinct sub-population of lymphocytes by their capacity to spontaneously lyse tumor cells ( 1 ). (frontiersin.org)
  • While CAR T cells, and T cells in general, are often effective in identifying and killing tumor cells , the precise mechanism by which the TCR works hasn't been clear," says the study's lead author, Kristine Brazin, Ph.D., of Dana-Farber and Harvard Medical School. (medicalxpress.com)
  • In recent years, tumor immunotherapy has achieved significant success in various cancers and has been one of the hotspots in the life sciences, especially immune checkpoint inhibitors and adoptive cellular therapy [ 3 ]. (hindawi.com)
  • Adoptive cellular therapy transmits the sensitized T cells to patients with low cellular immune function, which helps patients obtain antitumor immunity. (hindawi.com)
  • Cellular adoptive immunotherapy is a type of immunotherapy. (wikipedia.org)
  • A major application of cellular adoptive therapy is cancer treatment, as the immune system plays a vital role in the development and growth of cancer. (wikipedia.org)
  • Cellular adoptive therapy is another alternative for these patients. (wikipedia.org)
  • Cellular metabolic reprogramming is acknowledged as a hallmark of cancer, and emerging evidence suggests that elucidating the underlying mechanisms of how intratumoral Tregs acquire metabolic fitness and superior immunosuppression in the TME may contribute to clinical benefits. (biomedcentral.com)
  • Mechanisms of Natural Killer (NK) cell dysfunction within the tumor microenvironment. (encyclopedia.pub)
  • An additional inhibitory mechanism exploited by the tumor microenvironment is represented by the imbalance in immune checkpoint molecules, responsible for NK cell exhausted status. (encyclopedia.pub)
  • Here, we review tumor-NK cell interactions, discuss the mechanisms by which NK cells generate an antitumor immune response, and discuss NK cell-based therapeutic strategies targeting activating, inhibitory, and co-stimulatory receptors. (frontiersin.org)
  • Expanded understanding of the basic biology of T cell activation has enabled immunotherapy to combat cancer, and T cell metabolism now offers the opportunity to optimize and improve these therapeutic strategies. (elifesciences.org)
  • It is hoped that, with rapid development of nanomedicine in cancer immunotherapy, TAMs-focused therapeutic strategies may be anticipated to become an emerging immunotherapeutic modality for future clinical cancer treatment. (thno.org)
  • To determine the mechanisms of how innate immune activation via lymphodepletion potentiated antitumor T cell immunity, we utilized the pmel-1 melanoma mouse model. (biomedcentral.com)
  • We also discuss the mechanisms underlying Treg functional fitness in the TME, hoping to find potential approaches to reestablish proinflammatory circumstances by perturbing these metabolic programs, ultimately enhancing the efficacy of antitumor immunity. (biomedcentral.com)
  • How is the signal, which originates when the receptor links to a tumor antigen, transmitted through the cell membrane into the cell interior leading to cell activation? (medicalxpress.com)
  • This binding process leads to the release of IL-1α and activation of IL-1 receptor, promoting chemokines production and attracting other innate immune cells to kill AdV infected MFs [61]. (genemedi.com)
  • These include the T cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte-activation gene-3 (LAG-3), TIGIT, and B-and T-lymphocyte-associated protein (BTLA) receptors associated with T cell exhaustion and V-domain immunoglobulin suppressor of T cell activation (VISTA), a receptor found on tumor-infiltrating myeloid cells. (biomedcentral.com)
  • The first studies with tumor-infiltrating lymphocytes (TILs) were performed at the Surgery Branch in the National Institutes of Health. (wikipedia.org)
  • Intratumoral immunotherapy strategies for cancer based on interleukin-12 (IL-12)-encoding cDNA and mRNA are under clinical development in combination with anti-PD-(L)1 monoclonal antibodies. (unav.edu)
  • Finally, it retrospectively analyze the activation strategies and clinical relevance of existing γδ T cell adoptive immunotherapies. (explorationpub.com)
  • Consequently, adoptive transfer of autologous or allogeneic NK cells represents a novel opportunity in cancer treatment that is under clinical investigation. (encyclopedia.pub)
  • Thus, TAMs can be considered as a promising therapeutic target for improved immunotherapy, and TAMs-focused molecular targeting agents have made ideal progress in clinical practice. (thno.org)
  • Lastly, some severe challenges related to functional nanomedicines for TAMs-focused cancer immunotherapy are proposed, and some feasible perspectives on clinical translation of TAMs-associated anticancer immunonanomedicines are provided. (thno.org)
  • In clinical practice, cancer immunotherapies have been well developed in recent years, mainly including cytokine therapy (e.g. (thno.org)
  • CAR-T cell therapy has achieved outstanding progresses in clinical observations, which makes it even more attractive in the development of cancer adoptive immunotherapy. (ijbs.com)
  • As shown by multiplex tissue immunofluorescence and intravital microscopy, combined immunotherapy treatments enhance T cell infiltration and the intratumoral performance of T lymphocytes. (unav.edu)
  • However, the mechanisms behind this impaired outcome of ICI treatments in diabetic patients remain unknown. (nature.com)
  • Researchers must ensure reproducibility, efficacy and potency of cancer immunotherapy treatments before these reach the clinic. (technologynetworks.com)
  • For these reasons anti-PD-1 mediated immunotherapies are currently being explored as cancer treatments. (bioxcell.com)
  • PD-1 is transiently expressed on CD4 and CD8 thymocytes as well as activated T and B lymphocytes and myeloid cells. (bioxcell.com)
  • NK cell activation and the triggering of effector functions is governed by a complex set of activating and inhibitory receptors. (frontiersin.org)
  • First, γδ T cells exposed to complicated cytokine networks are potentially affected by multiple inhibitory mechanisms. (explorationpub.com)
  • Multiple mechanisms are implicated in such dysfunction, spanning from inhibition of recruitment to the tumor bed, activation of inhibitory processes, blowing up of activation signals, and deregulation of metabolism ( Figure 1 ). (encyclopedia.pub)
  • Lymphodepletion enhances adoptive T cell transfer (ACT) therapy by activating the innate immune system via microbes released from the radiation-injured gut. (biomedcentral.com)
  • Natural killer cells (NK) are innate lymphocytes endowed with the ability to recognize and kill cancer cells. (encyclopedia.pub)
  • Cancer immunotherapy consists of multiple approaches that harness and enhance the innate powers of the immune system to fight the disease. (technologynetworks.com)
  • The recent FDA approvals of the programmed cell death protein 1 (PD-1)-targeted checkpoint inhibitors pembrolizumab and nivolumab mark the latest successes in the rapidly expanding field of cancer immunotherapies. (frontiersin.org)
  • The major application of CAR-T immunotherapy is to treat hematological malignancies, such as multiple myeloma, chronic lymphocytic leukemia, acute lymphoblastic leukemia and lymphoma. (wikipedia.org)
  • T lymphocytes for adoptive cell therapy against hematological cancer. (upstate.edu)
  • According to current challenges, there is a need to explore innovative immunotherapies, maximize the tumor-killing efficacy of γδ T cells, and attenuate or eliminate tumor immunosuppression. (explorationpub.com)
  • Here, the underlying mechanisms of tumor immunosuppression caused by TAMs are first emphatically elucidated, and then the basic design of TAMs-focused immune-nanomedicines are discussed, mainly including diverse categories of nanomaterials, targeted and stimulus-responsive modifications, and TAM imaging in nanomedicines. (thno.org)
  • Collectively, our results identify how and when to administer TLR agonists to augment T cell-based immunotherapy in the absence or presence of host preconditioning for treatment of advanced malignancies. (biomedcentral.com)
  • The purpose is to deliver chemotherapy, immunotherapy, and/or radiation to eliminate malignancy, prevent rejection of new stem cells, and create space for the new cells. (medscape.com)
  • One of the key aspects for successful immunotherapy is to achieve a strong and stable antitumor immune response. (mdpi.com)
  • A summary of current TAMs-targeting immunotherapeutic mechanisms based on functional nanomedicines for TAMs elimination and/or repolarization is further presented. (thno.org)
  • To bypass resistance, combination treatment with immunotherapies and single or multiple TKIs have been shown to improve prognosis compared to monotherapy. (biomedcentral.com)
  • Combining tumor-specific adoptive T cell therapy to the aCTLA-4/aPD1/rIL2 or aCTLA-4/aPD1/aCD137 reg-imens enhances efficacy in a synergistic manner. (unav.edu)
  • While different methods exist to evaluate the efficacy of immunotherapy products, more efficient and robust in vitro assays are still required to ensure their safety and consistency. (technologynetworks.com)
  • Thus, it is imperative to develop more competent and safer immunotherapy approaches by optimizing the design of CAR vectors, exploring new targets, incorporating conditional safe switches and combining with other strategies. (ijbs.com)
  • Immunotherapy is among the most effective approaches for treating cancer. (mdpi.com)
  • In the setting of allogeneic hematopoietic stem cell transplantation, donor lymphocyte infusions are frequently given to treat relapse of hematologic malignancies. (ashpublications.org)
  • INTRODUCTION: Public health responses often lack the infrastructure to capture the impact of public health emergencies on pregnant women and infants, with limited mechanisms for linking pregnant women with their infants nationally to monitor long-term effects. (wisc.edu)
  • Nascent transformed cells elicit NK cell activation and are eliminated. (frontiersin.org)
  • Typically, CARs consist of a target binding domain, which is an extracellular domain that is specifically expressed by CAR-T cells, a transmembrane domain, and a signalling domain, which is an intracellular domain that provides an activation signal to T cells. (nature.com)
  • This review will discuss the metabolic changes that drive T cells into different stages of their development and how the TME imposes barriers to the metabolism and activity of tumor infiltrating lymphocytes. (elifesciences.org)
  • Natural Killer Cells in Cancer: Mechanisms of Dysfunction" Encyclopedia , https://encyclopedia.pub/entry/45851 (accessed November 29, 2023). (encyclopedia.pub)
  • IFNγ is primarily produced by activated lymphocytes including T, B, NK cells, and ILCs. (bioxcell.com)
  • However, the accumulation of evidence suggests that immunotherapy also induces severe and complex neurologic immune-related adverse events (ir-AEs) and even leads to immunotherapy-related death, which arouses the concern of clinicians. (hindawi.com)
  • His research is focused on the mechanisms that regulate the immunological response of T lymphocytes, especially strategies to manipulate those responses in clinically relevant areas, including autoimmunity, allergies, vaccinations, and tumor therapy. (euroacadti.eu)
  • By focusing on the critical roles of different metabolic programs, such as glycolysis, oxidative phosphorylation, fatty acid oxidation, fatty acid synthesis, and amino acid metabolism, as well as their essential regulators in modulating Treg proliferation, migration, and function, we hope to provide new insights into Treg cell-targeted antitumor immunotherapies. (biomedcentral.com)
  • Upon ligand binding, PD-1 signaling inhibits T-cell activation, leading to reduced proliferation, cytokine production, and T-cell death. (bioxcell.com)
  • B7-H1 and B7-H3, two members of the B7 family that are thought to regulate T-cell activation, are expressed in human non-small cell lung cancer (NSCLC). (oncotarget.com)
  • Additionally, induced co -expression of luciferase, EGFP, and the melanosomal antigen gp100 facilitates studies on the underlying immunological mechanisms. (unav.edu)
  • Additionally, Pdcd1 mRNA is expressed in developing B lymphocytes during the pro-B-cell stage. (bioxcell.com)
  • Finally, we will provide an overview of how utilizing an understanding of T cell metabolism may inform strategies to alter the TME or enhance T cell metabolism to strengthen the immunotherapy arsenal. (elifesciences.org)