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Immunomodulatory Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Cytokines (from the Greek Cyto for cell and Kines for movement) is the top-level name for a broad category of small proteins and glycoproteins (~5–20 kDa) important in cell signaling. They include the interferons, interleukins, lymphokines, chemokines, and tumor necrosis factor, but exclude hormones and growth factors (despite some terminological similarities and overlap). They are also known as Biological Response Modifiers (BRMs). This area of research is still highly active, and more cancer therapies based on this approach are likely to be developed in the future.
Cytokines
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Cytokines may be classified on the basis of their cell of origin, spectrum of activity, their target cells and the ligand–receptor interaction. Lymphokines are cytokines produced by lymphocytes, monokines by monocytes and interleukins (ILs) are cytokines released by leukocytes that have major effects on other white cells. Cytokines that cause proliferation and differentiation of stem cells are called colony stimulating factors (Table 57.1).
Macrophages As Effectors Of Cell-Mediated Immunity
Published in Hans H. Gadebusch, Phagocytes and Cellular Immunity, 2020
Although much emphasis is now placed on immunologically nonspecific lymphokines, immunologically specific factors may also have a role. There may be an element of specificity in macrophage-mediated resistance to some protozoa.135*136*139 Antibodies to Salmonella have been detected on macrophages from immunized mice.503*504 There have also been reports that RNA extracted from macrophages or other lymphoid cells can induce resistance in normal macrophages in vivo or in vitro.505*506 At first glance, it is difficult to see how such a mechanism could operate physiologically. One could, however, conceive that in vivo activation achieved in this way could be due to active immunization by immunogenic RNA507 while both in vivo and in vitro activation might be similar in mechanism to nonspecific activation by polynucleotides.342
Advances in the development of tumor-infiltrating lymphocyte therapy for advanced melanoma
Published in Expert Opinion on Biological Therapy, 2023
Interest in TILs as a therapeutic anti-cancer strategy was first established by Steve Rosenberg and team at the NCI [1]. Initial investigation focused on the use of lymphokine activated killer cells (LAKs) [4]. LAKs represent isolated peripheral blood leukocytes, which when stimulated ex vivo with IL-2, demonstrate the ability to lyse tumor cells, whilst sparing nonmalignant cells [4]. Subsequent efforts focused on isolation of specific lymphocyte populations beyond the peripheral compartment [5]. Following the successful isolation and expansion of lymphocytes from surgically resected tumor specimens, the first trial demonstrating the efficacy of adoptively transferred TILs in patients with metastatic melanoma was documented by Rosenberg et al in 1988 [1]. Twenty patients were enrolled; 15 treatment-naïve and 5 having received prior IL-2 therapy. Patients received a single lymphodepleting dose of cyclophosphamide at 25 mg/kg, 36 hours prior to TIL infusion, with a cell dose range of 3 × 1010- 75 × 1010. IL-2 at a dose of 100,000 IU/kg was then administered every 8 hours until dose-limiting toxicity occurred. Objective responses were observed in 60% (9/15) of treatment-naïve and 40% of IL-2 pre-treated patients respectively. Toxicity, although significant, was attributed to IL-2 and there were no treatment-associated deaths [1].
Combining the past and present to advance immuno-radiotherapy of cancer
Published in International Reviews of Immunology, 2023
Ioannis M. Koukourakis, Michael I. Koukourakis
The discovery of interferons in 1957 opened the field for the unveiling of a group of molecules, cytokines, and growth factors, that mediate immune cell communication and activities [25]. Leukocytes, fibroblasts and, also, cancer cells were soon shown to be the source of interferons (IFNs) [26, 27]. Experimental studies subsequently showed that IFNs have antitumor properties [28, 29], opening the field for clinical application of purified and recombinant IFNs in Oncology [30–32]. The biochemical separation of Interleukin-2 (IL-2) [33] and experimental studies that followed, revealed the potent therapeutic potential of this lymphokine that activates proliferation and killing activity of cytotoxic T-cells [34]. Following randomized clinical trials, IFN-α was approved for the treatment of melanomas and lymphomas, and IL-2 for the treatment of renal cancer [35, 36]. However, the overall benefit from cytokine therapy of solid tumors was far smaller than anticipated, and the frustration from immunotherapy attempts was evident in the ‘90s. The interest in tumor immunotherapy, however, had never been ceased, and this was recompensed by the encouraging results obtained during the past ten years from clinical trials with novel immune checkpoint inhibitors, and their approval for clinical use [37].
Immune dysregulation in primary immune thrombocytopenia patients
Published in Hematology, 2018
Jiakui Zhang, Qiuye Zhang, Yingwei Li, Lili Tao, Fan Wu, Yuanyuan Shen, Qianshan Tao, Xuanxuan Xu, Can Wu, Yanjie Ruan, Jiyu Wang, Jeffrey Wang, Yiping Wang, Zhimin Zhai
B cells can produce antiplatelet autoantibodies and cause platelet destruction in ITP patients. Several studies have shown that B cells may be higher in ITP patients than normal individuals [7,18]. As we know, the mechanism behind the production of antigen-specific antibodies by B lymphocytes is controlled by various regulatory agents [19]. The antigen should be recognized by B cells, APCs and CD4 + Th cells first, from which it will undergo proteolytic processes and be subsequently presented to Th cells. Afterwards, the Th cells become activated and secrete lymphokines, which stimulate antigen-specific B cells to produce and secrete antibodies. In our study, there were no significant differences in the number of B cells between our groups. This may due to the complex mechanism behind B cell activation, and the different functions in the subgroups of the B cell line. We will conduct more research into the B cell line subgroups within ITP in the future.