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Immunologically Mediated Diseases and Allergic Reactions
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Kim A. Campbell, Caroline C. Whitacre
Upon reexposure to the allergen, the Langerhans′ cells again process and present the antigen to the primed T cells, which initiate the elicitation phase of DTH in the skin. Activated, memory T cells release a number of soluble mediators termed cytokines. In particular, interferon gamma (IFNγ) activates macrophages and enhances their ability to eliminate the antigen. IFNy increases phagocytosis, antigen presenting efficiency, and microbicidal activity. Because it is a potent macrophage activating cytokine, IFNy is the most potent mediator of DTH reactions. IFNγ also increases the expression of adhesion molecules on endothelial cells and potentiates the release of proinflammatory cytokines and chemokines. This complex cascade of events results in the recruitment and activation of many T cells and macrophages in the local inflammatory site. Upon gross examination of the DTH reaction site, the area is erythematous and “indurated” or hard to the touch. Resolution of DTH reactions occurs after forty-eight to seventy-two hours, and the mechanism of suppression involves secretion of prostaglandin E2 and downregulatory cytokines, such as TGFβ and IL-10. Both TGFβ and PGE2 have inhibitory effects on IL-1 and IL-2 synthesis; whereas, IL-10 downregulates Class II molecules and inhibits antigen-specific proliferation of IFNy-secreting T cells.
Renal Cell Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Historically surgical removal of the involved kidney (cytoreductive nephrectomy) in patients presenting with metastatic RCC was undertaken for palliation of symptomatic primary tumors. Occasionally metastatic disease can be seen to regress spontaneously. What is not clear is whether removal of the primary tumor is beneficial to survival. Trials in the early immunotherapy era with interferon gamma did demonstrate some benefit. A combined analysis of two trials of nephrectomy prior to interferon gamma in highly selected fit patients demonstrated a weighted mean difference in median survival of 4.8 months (12.6 versus 7.8 months) in favor of the surgical arm.29
Tuberculosis and Human Immunodeficiency Virus Coinfection
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Charisse Mandimika, Gerald Friedland
A variety of interferon gamma release assays (IGRAs) are currently available. A recent meta-analysis suggested that IGRAs perform similarly to TST in PLWH50 and vary similarly in sensitivity and specificity related to the degree of immunosuppression. There are limited data on the use of IGRA in children under 5 years old and persons recently exposed to TB. Although sensitivity is equivalent to TSTs, IGRAS are preferred in persons who received Bacillus Calmette–Guérin (BCG) because they do not cross react with BCG and in persons who may not be able to return for a TST reading.
Vaccine development against Helicobacter pylori: from ideal antigens to the current landscape
Published in Expert Review of Vaccines, 2021
Irineu Dos Santos Viana, Maria Luísa Cordeiro Santos, Hanna Santos Marques, Vinícius Lima de Souza Gonçalves, Breno Bittencourt de Brito, Filipe Antônio França da Silva, Natália Oliveira e Silva, Fillipe Dantas Pinheiro, Adriano Fernandes Teixeira, Davi Tanajura Costa, Briza Oliveira Souza, Cláudio Lima Souza, Márcio Vasconcelos Oliveira, Fabrício Freire de Melo
The EpiVax/H. pylori vaccine is in the preclinical phase and is based on multi epitopes, which involves a DNA vaccination followed by a peptide-liposome and has resulted in therapeutic protection in mice [72]. This study with a total of 80 mice and monitoring of infection by real-time PCR, showed results that may indicate that a DNA-prime/peptide-boost vaccine designed to present multiple H. pylori epitopes has a positive efficacy when administered performed nasally in mice that were infected with H. pylori. The vaccine’s effectiveness was evaluated as a therapeutic option, which resulted in a broad immune response with high production of interferon-gamma. As a result, a significant reduction in colonization by H. pylori was found in the mucosa of the mice.
Immunotherapy in uveal melanoma: novel strategies and opportunities for personalized treatment
Published in Expert Opinion on Investigational Drugs, 2021
Christos Masaoutis, Stefania Kokkali, Stamatios Theocharis
Nevertheless, immunotherapy still constitutes a reasonable strategy, especially since UM seems to rely heavily on immune escape to survive. Indications that efficacious immune surveillance is feasible include anecdotal reports of total [58] or incomplete [59] regression of UM associated with signs of inflammation [59]; exceptionally long responders in the trials of immunotherapy combinations with OS of 5 years [60]; a lower risk of melanoma 10 years after yellow fever vaccination probably due to its resemblance to HERV-K MEL, a melanoma-specific antigen (including ocular melanoma) able to induce oligo- or monoclonal cytotoxic T-cell responses when presented by HLA-A2 [61]. Interestingly, differences in gene expression profile were recently reported between responders and non responders UM patients to immunotherapy [62]. Upregulation of interferon-gamma signature was observed in responders, providing preliminary evidence for potential patient selection and personalized administration of immunotherapy. After all, there is evidence of cytotoxic lymphocyte-mediated lysis of UM cells in vitro [63–65] and preferential usage of TCR gene Vα7 among UM TILs, as in antigen-specific T-cell response [6]. Of note, attraction of inflammation seems to be hardwired in a subset of UM (see §4). Therefore, novel strategies beyond current immune checkpoint inhibition aiming to boost immunorecognition and tumor sensitivity merit consideration.
Antitumor activity of the third generation EphA2 CAR-T cells against glioblastoma is associated with interferon gamma induced PD-L1
Published in OncoImmunology, 2021
Zhijing an, Yi Hu, Yue Bai, Can Zhang, Chang Xu, Xun Kang, Shoubo Yang, Wenbin Li, Xiaosong Zhong
Interferon gamma is a dimerized soluble cytokine critical for innate and adaptive immunity and is mainly secreted by activated T cells. IFN-γ plays a key role in the activation of cellular immunity and, subsequently, in the stimulation of the antitumor immune response. However, excessive IFN-γ production is one of the main sources of CAR-T cell toxicity.36,37 In addition, high IFN-γ levels in the TME can induce the overexpression of PD-L1 in tumor cells, which further binds to PD-1 in T cells and induces T cell exhaustion. This study observed that CAR-T cells secreted an extremely high level of IFN-γ had weak anti-tumor activity against GBM in vitro and in vivo. These findings indicate that excessively high IFN-γ production can be used as a negative evaluation criterion for CAR-T cells. Furthermore, PD-1 knockout combined with CAR-T therapy is a good strategy to overcome the IFNγ-PD-L1-PD-1 obstacle.