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The Inducible System: History of Development of Immunology as a Component of Host-Parasite Interactions
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
The first hints at the existence of hormones mediating the immune response to antigen came in the mid 1960s. Experiments demonstrated that conditioned medium (medium in which lymphocytes had been stimulated to divide) was mito-genic. When conditioned medium was added to a culture of T lymphocytes, they were stimulated to divide. Since the responding cells were T cells, the term T cell growth factor (TCGF) was coined to describe this activity Since lymphocytes were the source of this mitogenic activity, the more general term lymphokine was used to describe the class of molecule.
Therapy with lnterleukin-2 and Tumor-Derived Activated Lymphocytes
Published in Ronald H. Goldfarb, Theresa L. Whiteside, Tumor Immunology and Cancer Therapy, 2020
Given the accumulated data from nearly 20 years of immunotherapy, it is now clear that T lymphocytes can mediate significant antitumor responses in man. A limiting factor has always been the ability to expand T cells, whether they were derived from the peripheral blood, lymph node, spleen, or tumor. With rIL-2, a T cell growth factor, it is now feasible to expand T cells from any of these sources, some of which have demonstrated clinical efficacy as antitumor effectors in murine models and in man.
The Thymus, Immune System, and Aging
Published in Nate F. Cardarelli, The Thymus in Health and Senescence, 2019
THF (thymus humoral factor) enhanced the GvH response in aged mice.50 This hormone also causes T-cell growth factor production to rise in old mice,182 prevents sensitization against self-antigens, and thus retards autoantibody build-up.183 It also seems to mediate, at least in part, thymus involvement in discrimination between self and nonself. In clinical studies with 72 immune depressed patients, THF was found to provide no less than partial improvement to all excepting SCID patients.183 Two subjects with rheumatoid arthritis were cured. Some improvement was seen in CID (congenital immune defects) patients. Excellent immune recovery was noted with patients suffering from viral diseases—herpes zoster, herpes simplex, varicella, and measles. However, THF is of no value to SCID (severe combine immune deficiency) since its probable target, stem cell precursors, are not present. Obviously THF cannot mature what is not there. In clinical studies of 20 children with severe measles, THF helped prevent typical secondary complications, such as herpes.184
Pathogenicity and virulence of human T lymphotropic virus type-1 (HTLV-1) in oncogenesis: adult T-cell leukemia/lymphoma (ATLL)
Published in Critical Reviews in Clinical Laboratory Sciences, 2023
Sanaz Ahmadi Ghezeldasht, David J. Blackbourn, Arman Mosavat, Seyed Abdolrahim Rezaee
Altogether, these questions have yet to be clearly explained: how does Tax orchestrate HTLV-1-infected CD4+ T cell activities? Which molecules are promoting infected cell proliferation, cancer development, and progression? Maybe in the early stage of transformation, Tax induces IL-2 and IL-2R production and indirectly activates the JAK/STAT and the JAK/PI3K/AKT/mTORC1 pathway in IL-2-responsive ATLL cells (Figure 5). It is well-known that IL-2, the primary T cell growth factor, participates in T cell malignancy [153–155]. PI3K/Akt pathway contains around eight members that regulate cell survival, proliferation, and transformation in many different malignancies [156]. In the case of HTLV-1 infection, PI3K/Akt pathway has been reported to act as a Tax and NF-κB activator (mainly non-canonical pathway) in ATLL cells. Remarkably, several reports have suggested the implication of the PI3K pathway in ATLL as a common feature of Tax and HBZ-transformed cells. Treating IL-2-independent HTLV-1-transformed T-cells with PI3 kinase inhibitors results in p27KIP1-dependent cell cycle arrest, inhibiting cancerous conditions [157,158]. In our system biology work, the most differential pathway involved in cell transformation is PI3K in ATLL compared to AC and HAM/TSP [87].
Response to systemic therapy in locally advanced and metastatic renal cell carcinoma: can it be predicted?
Published in Expert Review of Anticancer Therapy, 2021
Javier González, Jeffrey J Gaynor, Gaetano Ciancio
Cytokines are substances produced by immune cells that enable signaling between different cell types using a ligand-receptor system, which in turn may induce the activation/inhibition of a number of regulatory proteins, or exert a direct effect on the cells of various tissues. These molecules, particularly interferon (IFN) and interleukin-2 (IL-2), were studied in the past as potential effectors in mRCC to increase the potential chance for survival. Besides their logical stimulation of different immune cells, other biologic effects observed with increasing doses of IFN included certain antiangiogenic activity, downregulation of a number of oncogenes, and antiproliferative potential. On the other hand, IL-2 was characterized as a T-cell growth factor given its ability to expand T-cell, natural killer (NK), and lymphokine-activated killer cell populations. This capability was observed to play a crucial dose-dependent anti-tumoral role, and was thus used as systemic therapy for mRCC [4].
IL-6 and IL-8 as Prognostic Factors in Peritoneal Fluid of Ovarian Cancer
Published in Immunological Investigations, 2020
Isac Souza Silva Rodrigues, Agrimaldo Martins-Filho, Douglas Côbo Micheli, Cid Almeida de Lima, Beatriz Martins Tavares-Murta, Eddie Fernando Candido Murta, Rosekeila Simões Nomelini
Due to the potent activity of IL2 as a T cell growth factor in vitro, this cytokine has been extensively studied. This activity provides an environment for boosting immunity, or a target for antagonizing unwanted responses, transplant rejection, and autoimmune diseases (deLeeuw et al. 2015; Malek and Castro 2010). In a study of mice with ovarian cancer, the use of IL-2 as monotherapy or as an adjuvant in adoptive therapy through intraperitoneal administration of IL-2 produced a 25% objective response rate in early clinical trials (deLeeuw et al. 2015; Rosenberg 2014). In our study, IL2 levels were not related to any of the prognostic factors studied, as was the study by Martins-Filho et al., in the intracellular fluid of malignant ovarian lesions (Martins-Filho et al. 2017), and Sanguinete et al. who measured serum cytokines in ovarian cancer patients (Sanguinete et al. 2017).