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Characteristics, Events, and Stages in Tumorigenesis
Published in Franklyn De Silva, Jane Alcorn, The Elusive Road Towards Effective Cancer Prevention and Treatment, 2023
Franklyn De Silva, Jane Alcorn
In carcinogenesis, the immune system can play a dual role, either initiating wound healing-related pathway signaling to assist in fostering an environment favorable to cancer or eliminating cells that have undergone malignant transformation due to early cancer-initiating events (e.g., immunoediting) [959–961]. Cancers associated with immunosuppression might be a consequence of tumor viruses [929, 946, 954, 962]. Aging and loss of immune surveillance for epitopes of specific viral cytotoxic T-cells can result in the viral promotion of cancers [946, 963, 964]. Common to tumors of persistent latent or pseudo-latent infections is the discontinuation of tumor virus replication that form infectious virus particles (i.e., lytic replication), which is an important strategy for immune evasion [946]. Viruses which typically exist as naked nucleic acids in a plasmid or episome inside the cell rely on the machinery of the host cell to replicate upon cell division [946, 965]. Host cell death is triggered as a consequence of the productive replication of viruses (i.e., cytopathic effect); consequently, virus latency may seem to best explain the link with virus-mediated tumorigenesis [946, 965]. Yet, this effect is harnessed to target and eliminate cancer cells through cell death, which underlies the general premise behind viral oncolytic therapies used in immunotherapy (i.e., oncolytic virotherapy) [946, 965–968]. Here, oncolytic viruses (OV) are used to preferentially remove neoplastic cells, sparing healthy cells (e.g., HSV-1 based OV) [968–971].
The Inducible Defense System: The Induction and Development of the Inducible Defence
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Michael A. Hickey, Diane Wallace Taylor
T cells have a variety of functions and can be divided into three functionally different subsets (Table 8.1). These include cytotoxic T cells, T helper 1 (Th1) cells that participate in inflammation, and T helper 2 (Th2) cells that provide help for antibody production. The primary role of cytotoxic T cells is to recognize foreign cells, (i.e., in skin grafts), tumors, and virus-infected cells and kill them. These cells express the surface marker CD8. Helper T cells express the surface marker CD4 and interact directly or produce soluble chemical signals called cytokines, which influence the activation and differentiation of other cells. Th1 cells (T helper 1) produce cytokines that activate cells involved in inflammation. For example, Th1 cells produce the cytokine interferon-γ (IFN-γ) which increases the ability of macrophages and neutrophils to kill invading pathogens. On the other hand, Th2 cells (T helper 2) interact with B cells to stimulate their activation and differentiation into plasma cells and are required for the production of antibodies.
The immune and lymphatic systems, infection and sepsis
Published in Peate Ian, Dutton Helen, Acute Nursing Care, 2020
Michelle Treacy, Caroline Smales, Helen Dutton
differentiation into one of the following, depending on the nature of the antigen: T helper cells respond by secretion of interleukins or messenger proteins, promoting the proliferation of B lymphocytes, other T lymphocytes and natural killer cells to phagocytose.T helper cells also promote the maturation of B cells and T lymphocytes, once interleukins have been released.Cytotoxic T cells recognise and destroy cells infected by viruses and cells altered by cancer.Memory cells continue to exist after an infection has resolved. They remember antigens and quickly expand if the infection is encountered again.T suppressor or regulatory cells downregulate the immune response when the objective has been achieved.
Generation of a novel fully human non-superagonistic anti-CD28 antibody with efficient and safe T-cell co-stimulation properties
Published in mAbs, 2023
Abdullah Elsayed, Christian Pellegrino, Louis Plüss, Frederik Peissert, Ramon Benz, Franziska Ulrich, Gudrun Thorhallsdottir, Sheila Dakhel Plaza, Alessandra Villa, Jacqueline Mock, Emanuele Puca, Roberto De Luca, Markus G. Manz, Cornelia Halin, Dario Neri
Cytotoxic T cells are key mediators of the adaptive immune system to fight cancer. The discovery of the T-cell receptor (TCR) revealed the mechanism of how T cells become activated upon antigen recognition.1–3 TCR engagement is initiated by recognizing antigenic peptides, such as tumor antigens, presented by the major histocompatibility complex (MHC) on antigen-presenting cells (APCs) and tumor cells.4,5 TCRs lack an intracellular signaling domain. Therefore, their association with CD3 and other co-receptors (e.g., CD4, CD8) is necessary to trigger an activation signal cascade, referred to as “signal 1.”6–9 However, signal 1 alone is typically insufficient for the full activation of T cells. The absence of an additional signal induces T-cell anergy and impairs T-cell activity.10,11 The CD28 receptor provides a crucial costimulatory signal that enhances T-cell proliferation, survival, and production of key cytokines (e.g., IL-2); this costimulatory effect is referred to as “signal 2.”12–15 CD28 is a homo-dimeric glycoprotein that is constitutively expressed on the surface membrane of most T cells (around 95% of CD4+ and 50% of CD8+ T cells).16 In the immune synapse, CD28 binds to its counter receptors, CD80 and CD86, primarily expressed on APCs.17–21
Recent progress in antibody-based therapeutics for triple-negative breast cancer
Published in Expert Opinion on Drug Delivery, 2022
Wen-Jing Ning, Xue Liu, Hong-Ye Zeng, Zhi-Qiang an, Wen-Xin Luo, Ning-Shao Xia
The PD1/PD-L1 axis is the quintessential immune checkpoint pathway. PD1 is a type I transmembrane protein preferentially expressed in immune cells such as T cells, B cells, natural killer (NK) cells and activated monocytes and belongs to the CD28 superfamily [49]. The ligand PD-L1 is a member of the B7 family of antigen presentation costimulatory/coinhibitory molecules and is expressed in most tumour cells and some host cells. In the normal immune system, cytotoxic T cells can recognize mutated cancer cells and initiate their programmed cell death. To prevent excessive activation of normal cells by accident, PD1 inhibits the function of T lymphocytes by binding to the ligand PD-L1/PD-L2, thereby inhibiting the autoimmune response and maintaining the immune balance of the entire body [50]. However, tumour cells can confuse cytotoxic T lymphocytes (CTLs) by overexpressing PD-L1 themselves, sending an inhibitory signal to the CTLs [51]. Studies have confirmed that PD1-positive tumour-infiltrating lymphocytes (TILs) are associated with poor prognosis and OS of breast cancer, suggesting that researchers can modulate the immunosuppressive tumour microenvironment by blocking the PD-1/PD-L1 signalling pathway and thereby enhancing the antitumour immune effect [52].
Prospects for CAR T cell immunotherapy in autoimmune diseases: clues from Lupus
Published in Expert Opinion on Biological Therapy, 2022
Marko Radic, Indira Neeli, Tony Marion
Approximately one in 14 people will, sometime during their lifetime, experience one of the known autoimmune disorders [1]. Autoimmunity arises in myriad ways and results in strikingly different pathologies. Dozens of clinical diagnoses for autoimmune disorders are possible and include familiar ones, such as rheumatoid arthritis, multiple sclerosis, type I diabetes, psoriasis, and immune vasculitis, as well as dozens of less frequent autoimmune diseases or syndromes [2]. The defining signs of many autoimmune diseases give clues to the targets of autoimmunity. Autoimmune reactivity thus defines many of the most characteristic features of autoimmune disorders. Destruction of islet cells in the pancreas leads to the insulin insufficiency of diabetes [3], the attack on myelin sheaths of neurons results in the neuropathology of multiple sclerosis [4], and the destruction of cartilage and bone contorts articular joints in rheumatoid arthritis [5]. Mechanisms of autoimmunity may involve the sudden appearance of autoantibodies, the activation of self-reactive cytotoxic T cells, the induction of self-sustaining, chronic inflammation, or a combination of contributing factors that overlap at different stages of pathogenesis in these disorders [6]. Manifestations of each autoimmune disease may be further modified by intrinsic factors or environmental contributions [2].