In addition to their known cytotoxic effects, chemotherapeutic agents can trigger cytokine production in tumor cells. Moreover, many chemotherapeutic agents are potent pro-oxidative stressors. Although the lipid mediator platelet-activating factor (PAF) is synthesized in response to oxidative stress, and many epidermal carcinomas express PAF receptors (PAF-R) linked to cytokine production, it is not known whether PAF is involved in chemotherapeutic agent-induced cytokine production. These studies examined the role of the PAF system in chemotherapy-mediated cytokine production using a model system created by retroviral-mediated transduction of the PAF-R-negative human epidermal carcinoma cell line KB with the human PAF-R. The presence of the PAF-R in KB cells resulted in augmentation of the production of cytokines IL-8 and TNF-alpha induced by the chemotherapeutic agents etoposide and mitomycin C. These effects were specific for the PAF-R, as expression of the G protein-coupled receptor for fMLP did not affect chemotherapeutic agent-induced cytokine production. Moreover, ablation of the native PAF-R in the epithelial cell line HaCaT using an inducible antisense PAF-R strategy inhibited etoposide-induced cytokine production. Oxidative stress and the transcription factor NF-kappaB were found to be involved in this augmentative effect, because it was mimicked by the oxidant tert-butyl-hydroperoxide, which was blocked both by antioxidants and by inhibition of the NFkappaB pathway using a super-repressor IkappaBM mutant. These studies provide evidence for a novel pathway by which the epidermal PAF-R can augment chemotherapy-induced cytokine production through an NF-kappaB-dependent process.
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http://dx.doi.org/10.4049/jimmunol.172.10.6330 | DOI Listing |
Nat Med
January 2025
BioNTech US, Cambridge, MA, USA.
New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.
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January 2025
CIRI, Centre International de Recherche en Infectiologie, (Team Lyacts), Univ Lyon, INSERM, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.
Resting natural killer (NK) cells display immediate effector functions after recognizing transformed or infected cells. The environmental nutrients and metabolic requirements to sustain these functions are not fully understood. Here, we show that NK cells rely on the use of extracellular pyruvate to support effector functions, signal transduction and cell viability.
View Article and Find Full Text PDFExp Cell Res
January 2025
Department of Plastic Surgery, The First Affiliated Hospital of Anhui Medical University, Anhui 230032, China. Electronic address:
Keloids are disfiguring proliferative scars, and their pathological mechanisms are still unclear. We have previously established that FoxC1 plays a significant role in rheumatoid arthritis and osteoarthritis, but its molecular mechanisms in pathological scar formation remain elusive. In this study, we analyzed keloid tissue characteristics using HE staining and immunohistochemistry, revealing abnormal expression of FoxC1 and Notch3 in keloids.
View Article and Find Full Text PDFTransl Oncol
January 2025
Department of Biological Sciences, Research Center of Ecomimetics, Chonnam National University, Gwangju 61186, South Korea. Electronic address:
Ataxia Telangiectasia Mutated (ATM) is a protein kinase traditionally known for its role in DNA damage response and cell cycle regulation. However, emerging research has revealed its multifaceted and crucial functions in the immune system. This comprehensive review explores the diverse roles of ATM in immune regulation, from lymphocyte development to its involvement in cancer immunotherapy.
View Article and Find Full Text PDFMicrobiol Res
December 2024
School of Medical Laboratory, Shandong Second Medical University, Weifang 261053, China. Electronic address:
Non-tuberculous Mycobacteria (NTM) are found extensively in various environments, yet most are non-pathogenic. Only a limited number of these organisms can cause various infections, including those affecting the lungs, skin, and central nervous system, particularly when the host's autoimmune function is compromised. Among these, Non-tuberculous Mycobacteria Pulmonary Diseases (NTM-PD) are the most prevalent.
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