Transposable elements (TEs) are often expressed at higher levels in tumor cells than normal cells, implicating these genomic regions as an untapped pool of tumor-associated antigens. In ovarian cancer (OC), protein from the TE ERV-K is frequently expressed by tumor cells. Here we determined whether the targeting of previously identified epitope in the envelope gene (env) of ERV-K resulted in target antigen specificity against cancer cells. We found that transducing healthy donor T cells with an ERV-K-Env-specific T cell receptor construct resulted in antigen specificity only when co-cultured with HLA-A*03:01 B lymphoblastoid cells. Furthermore, in vitro priming of several healthy donors with this epitope of ERV-K-Env did not result in target antigen specificity. These data suggest that the T cell receptor is a poor candidate for targeting this specific ERV-K-Env epitope and has limited potential as a T cell therapy for OC.
© 2024. The Author(s).

A possible explanation for chronic inflammation in HIV-infected individuals treated with anti-retroviral therapy is hyperreactivity of myeloid cells due to a phenomenon called "trained immunity." Here, we demonstrate that human monocyte-derived macrophages originating from monocytes initially treated with extracellular vesicles containing HIV-1 protein Nef (exNef), but differentiating in the absence of exNef, release increased levels of pro-inflammatory cytokines after lipopolysaccharide stimulation. This effect is associated with chromatin changes at the genes involved in inflammation and cholesterol metabolism pathways and upregulation of the lipid rafts and is blocked by methyl-β-cyclodextrin, statin, and an inhibitor of the lipid raft-associated receptor IGF1R. Bone-marrow-derived macrophages from exNef-injected mice, as well as from mice transplanted with bone marrow from exNef-injected animals, produce elevated levels of tumor necrosis factor α (TNF-α) upon stimulation. These phenomena are consistent with exNef-induced trained immunity that may contribute to persistent inflammation and associated co-morbidities in HIV-infected individuals with undetectable HIV load.
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Lymphopenia, T cell subgroup changes, and cytokine level differences are important in the early diagnosis and treatment of Covid-19 cases and similar pandemics. We aimed to investigate the T cell, monocyte subgroups, and cytokine differences according to disease severity. A total of 46 volunteers were included in the study. According to disease status, there were three groups (control, mild, and severe). The age, gender, smoking status, temperature, heart rate and oxygen saturation, complete blood count, C-reactive protein (CRP) was noted, and flow cytometric analyses were performed for T cell and monocyte subgroups, and cytokine levels. Temperature, heart rate, SPO2 , white blood cell (WBC), lympocyte count, trombocyte count, neutrophil/lymphocyte ratio, D-dimer and CRP levels, lymphocyte %, lymphocyte/monocyte rate, monocyte subtypes (%), CD3+ , CD4+ , CD8+ cell counts, interleukin (IL)-1β, TNF-alpha, monocyte chemoattractant protein (MCP)-1, IL-6, IL-8, IL-10, IL-18, IL-23 were significantly different between groups. CRP, IL-8, neutrophil/lymphocyte ratio, NK cells (%) have positive correlation and negative correlation was observed at lymphocyte (count), lymphocyte (%), lymphocyte/monocyte, classical monocyte (%), lymphocyte (count), CD3+ (count), CD4+ (count). As conclusion, lymphocyte (%), Lymphocyte (count), CRP levels, CD3+ and CD4+ cell counts strongly correlate with disease severity are valuable parameters for determining the prognoses of Covid-19.
© 2022 Wiley Periodicals LLC.

To evaluate the changes of cytokines and immune cells after Intra-articular hyaluronic acid(IAHA)injections in patients with knee osteoarthritis (KOA).
Sixteen patients were included in the study, with a total of 65 IAHA injections. The Numeric Rating Scale (NRS) and Lysholm scores were evaluated at each visit. The immune cells and 14 cytokines of synovial fluid were analyzed at each visit. The association between immune cells and cytokines were examined.
IL-6 and IL-8 were the most common cytokines in the synovial fluid of KOA patients. The synovial fluid was orchestrated by macrophages (69%) and Lymphocytes (18%). Neutrophils were less to count of the total cell population (< 2%). The cytokines decreased significantly after the first injection and then tended to be stable. Lymphocytes increased a lot, while Macrophages decreased in the early stage, then increased after multiple injections. The proposition of M1 decreased in the early stage, then increased after multiple injections, while M2 increased consistently. M1 and M2 were positively associated with IL-6 and IL-8.
The synovial fluid of KOA patients was orchestrated by macrophages (69%) and Lymphocytes (18%) and cytokines like IL-6 and IL-8. IAHA may play an anti-inflammatory functional role through the decreased production of IL-6 and IL-8 by macrophages through polarization. The results from this study partially revealed the effect of IAHA on cytokines and immune cells change in KOA patients, and therapies targeting pathogenic cytokines and immune cells might be used to attenuate the knee joint inflammation and release pain.
ChiCTR2100050133; date registered 17 August 2021.
© 2022. The Author(s).

Pancreatic ductal adenocarcinoma (PDAC) tumors are characterized by a desmoplastic reaction resulting in dense deposition of collagen that is known to promote cancer progression. A central mediator of protumorigenic collagen signaling is the receptor tyrosine kinase discoid domain receptor 1 (DDR1). DDR1 is a critical driver of a mesenchymal and invasive cancer cell PDAC phenotype. Previous studies have demonstrated that genetic or pharmacologic inhibition of DDR1 reduces PDAC tumorigenesis and metastasis. Here, we investigated whether DDR1 signaling has cancer cell nonautonomous effects that promote PDAC progression and metastasis. We demonstrate that collagen-induced DDR1 activation in cancer cells is a major stimulus for CXCL5 production, resulting in the recruitment of tumor-associated neutrophils (TANs), the formation of neutrophil extracellular traps (NETs), and subsequent cancer cell invasion and metastasis. Moreover, we have identified that collagen-induced CXCL5 production was mediated by a DDR1/PKCθ/SYK/NF-κB signaling cascade. Together, these results highlight the critical contribution of the collagen I-DDR1 interaction in the formation of an immune microenvironment that promotes PDAC metastasis.