IFNG expression

ECH upregulates the expression of inducible PD-L1 through the JAK/STAT1/IRF1 signaling pathway, enhances T cell function, and reshapes the tumor immune landscape into an anti-tumor phenotype. Importantly, ECH markedly enhances the efficacy of ICB treatment, indicating its potential application in anti-tumor therapy.

This observation indicates their promising potential as immunomodulatory therapies for cervical cancer cells. Nevertheless, additional investigation is imperative to comprehensively comprehend the fundamental mechanisms and refine therapeutic strategies involving PBMCs and mesenchymal stem cells.

Furthermore, a modified huCD39 mAb-secreting CAR-T cell has been generated, exhibiting superior efficacy against ovarian cancer. This provides a promising strategy for optimizing immunotherapies in ovarian cancer and potentially other malignancies.

Muscle-specific Nrf2 knockout in mice attenuated EAM-induced muscle weakness by inhibiting CCL5 mRNA expression, CD8+ T-lymphocyte migration and IFN-γ mRNA expression in muscles. These results provide further evidence for the potential therapeutic targeting of Nrf2 to mitigate EAM-induced muscle weakness.

In summary, these results suggested that the Qingrexiaoji recipe regulated M2 macrophage polarization by regulating miR-29a-3p/HDAC4, providing a different and innovative treatment for gastric cancer.

The clinical efficacy of neoadjuvant IT TAVO-EP + nivolumab is promising with 80% of patients achieving an MPR. Evidence of potent immune activation both systemically and within the TME along with a favorable safety profile supports the activity of local IL-12 and anti-PD1 based regimens.

2DG dose-dependently induced the unfolded protein response, suggesting a possible role in increased IFN-γ secretion, possibly by increasing the ER folding capacity for IFN-γ via increased chaperone expression. Overall, low-dose, short-term 2DG exposure could potentially improve the T cell anti-tumor response.

Immunotherapy involving Dicrocoelium eggs primarily induces a Th2 response and modulates IFN-γ, contributing to reduced inflammation in colitis. Thus, this approach could be a promising therapeutic strategy for alleviating inflammation in IBD.

P2, N=50, Recruiting, National Cancer Centre, Singapore | Trial completion date: Aug 2024 --> Feb 2025 | Trial primary completion date: Aug 2024 --> Feb 2025

Our findings uncovered the mechanism by which LMP1 interacts with ALIX and PD-L1 to form a trimolecular complex, facilitating PD-L1 loading into ALIX-dependent sEV secretion pathway, ultimately inhibiting the anti-tumor immune response in NPC. This highlights a novel target and prognostic marker for NPC immunotherapy.

In line, silencing of GRASLND under IFNγ enhanced the expression of IFNγ-stimulated genes, including HLA-I antigen presentation, demonstrating suppressive activity of GRASLND on IFNγ signaling. Our findings demonstrate that in differentiated melanomas elevated expression of GRASLND interferes with anti-tumor effects of IFNγ, suggesting a role of GRASLND in tumor immune evasion.

WD-3 enhanced the immunotherapeutic efficacy of anti-PD-1 by modulating the intestinal microbiota in an orthotopic model of GC mice.

Mechanistically, ZFP36L1 binds to the adenylate uridylate-rich element in the 3' untranslated region (3'UTR) of HDAC3 mRNA, exacerbating its mRNA decay, and thereby facilitating PD-L1 abnormal transcriptional activation. Collectively, our findings provide mechanistic insights into the role of the SPI1-ZFP36L1-HDAC3-PD-L1 signaling axis in orchestrating immune escape mechanisms in GC, thereby offering valuable insights into the potential targets for immune checkpoint therapy in GC management.

Overall, we demonstrated that IL-2 improves insulin sensitivity through two mechanisms: direct action on CD4 + T cells and via the neuro-immune axis triggered by hypothalamic microgliosis.

The inhibitory effect of VSIG-3/IGSF11 silencing on A2058 melanoma cell progression, along with the alteration of T cell cytokines towards a pro-inflammatory phenotype, suggests that VSIG-3/IGSF11 is primarily involved in melanoma progression and modulating immune responses. Therefore, it may be a valuable target for immunotherapy in melanoma patients.

The absence of IFNα2A significantly reduced the levels of latency and T cell exhaustion but not time of reactivation compared with control mice. Our results suggest that blocking IFNα2A expression may be a useful tool in reducing latency and the subsequent side effects associated with higher levels of latency.

This study has revealed lung cancer cell-conditioned media to modulate neutrophil functions through regulating factors, such as IL-8, thereby affecting immune regulation and tumor progression in the lung cancer microenvironment.

Mice achieving remission through NBTXR3 + PRT + αPD1 exhibited a robust memory immune response, effectively inhibiting growth of subsequent tumors from three distinct lung cancer cell lines. Proton IRT combined with NBTXR3 offers enhanced tumor control and survival rates over photon-based treatments in managing αPD1-resistant lung cancer, indicating its potential as a potent systemic therapy.

We demonstrated that JAKi prevent GM-CSF-induced CEACAM1 expression in neutrophils, and JAKi-induced inhibition depends on their selectivity against JAK isoforms. These findings suggest that JAKi can modulate the expression of CEACAM1 in cytokine-activated neutrophils, thereby limiting their activation.

Intranasal instillation of EI137 and EI341 exhibited anti-allergic and anti-inflammatory effects, influenced by Th1 and Th2 inflammatory cytokines. These lidocaine analogs suppressed DP-induced sinonasal mucosal inflammation, inflammatory cell infiltration, and mucus hypersecretion.

Although PBMC viability had increased, there was no evidence of enhanced T-cell activation. This system can be used to identify additional factors required to promote activation of naïve devil T-cells in vitro.

IDO-producing tumors show a high total IDO immunostaining score, and thus, using IDO inhibitors, such as Epacadostat, Navoximod, and L isomer of 1-methyl-tryptophan, seems an important modality for cancer treatment...Antitumor effects of imatinib are enhanced by increasing T-cell effector function in the presence of IDO inhibition. Combining IDO targeting with chemotherapy, radiotherapy and/or immunotherapy, may be an effective tool against a wide range of malignancies. However, there are some controversial results regarding the efficacy of IDO1 inhibitors in cancer treatment.

Herein, an immunotherapeutic hydrogel booster (GelMA-CJCNPs) was developed to prevent postoperative tumor recurrence and promote wound healing by incorporating ternary carrier-free nanoparticles (CJCNPs) containing chlorine e6 (Ce6), a BRD4 inhibitor (JQ1), and a glutaminase inhibitor (C968) into methacrylic anhydride-modified gelatin (GelMA) dressings...Moreover, GelMA-CJCNPs demonstrated satisfactory photodynamic antibacterial effects against Staphylococcus aureus infections, thereby promoting postsurgical wound healing. Hence, this immunotherapeutic hydrogel booster, as a facile and effective postoperative adjuvant, possesses a promising potential for inhibiting tumor recurrence and accelerating skin regeneration.

CXCL9 + macrophages and dendritic cells and CXCL12-expressing stromal cells likely recruit CXCR3/CXCR4-expressing NK and T cells and CXCR7 + HLA-E HIGH tumor cells. NK and CD8 T cells remain functional within BCG-unresponsive tumors but are inhibited by HLA-E and PD-L1, providing a framework for combined NKG2A and PD-L1 blockade strategy for bladder-sparing treatment of BCG-unresponsive NMIBC.

In the co-culture of Hep3B/OS-8/hPD-L1 cells and CD3+ T cells assay, III-4 relieved the inhibition of PD-L1 on PD-1 and promoted the expression of IFN-γ, which shared a comparable effect to that of the PD-1 monoclonal antibody Pembrolizumab (5 μg/mL). Moreover, compound III-5, an ester prodrug derived from III-4, demonstrated significant antitumor effects in the hPD-L1-MC38 C57BL/6 mouse model (TGI: 49.6 %) by oral administration. These findings suggest that compound III-5 holds promise as an inhibitor of the PD-1/PD-L1 interaction for cancer immunotherapy.

In xenograft mice injected with MPNST cells, IFN-γ treatment successfully suppressed tumor progression with increased IFITM1 expression and decreased Ras and ERK1/2 activation in tumor tissues. Collectively, these results suggest that IFITM1 is closely involved in MPNST pathogenesis and that IFN-γ is a good candidate for the therapeutic treatment of MPNSTs in NF1.

Molecular docking indicated high-affinity binding of the proteins encoded by these genes with JQ1. In conclusion, our study reveals the crucial role of activated DCs in ccRCC, offering new insights into predicting immune response, targeted therapy effectiveness, and prognosis for ccRCC patients.

The CXCL-9,-10,-11/CXCR3 axis, dependent on IFN-γ signaling activity, was overexpressed in primary breast cancer samples of patients who developed brain metastasis. The data support a role for T-lymphocytes and the IFN-γ pathway in the formation of brain metastasis of ER-breast cancer, and offer targets to design future therapies for preventing breast cancer cells to cross the BBB.

Cytokines such as TNF-α, IL-2, IL-6, IFN-γ, CRP, and D-D are aberrantly expressed in children with MPP and are associated with the severity of the disease. These cytokines have high diagnostic value and can serve as reference indicators for clinical, especially prognostic assessment of the severity of (pediatric) MPP.

In our study, we investigated how phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway inhibitors (TAK-228, everolimus and TAK-117) affect PD-L1 expression and function in preclinical bladder cancer cell models. These preclinical findings suggest that mTOR inhibition with TAK-228 can increase PD-L1 levels, potentially impacting the specific immune response against UC cells. This highlights the rationale for exploring the combination of mTOR inhibitors with ICIs in patients with advanced UC.

Therefore, the data suggest that the GBM microenvironment controls tryptophan levels by regulating IDO-1 expression, which plays a critical role in immune suppression. These findings support the use of immune therapy in combination with IDO-1 inhibitors or tryptophan supplementation as a potential treatment strategy.

We show that IDO1 inhibition delays tumourigenesis in Dock2 knockout mice, and we confirm that this pathway is conserved across species as IDO1 expression is elevated in human IBD-CRC and in sporadic CRC cases with mutated DOCK2. Together, these data demonstrate a previously unidentified tumour suppressive role of DOCK2 that limits IFNγ-induced IDO1 expression and cancer progression, opening potential new avenues for therapeutic intervention.

Single-cell ATAC-seq data analysis revealed increased Mir221/222 gene activity in pathogenic SF subclusters and transcriptional regulation by Rela, Relb, Junb, Bach1, and Nfe2l2. Our results establish an SF-specific pathogenic role of Mir221/222 in arthritis and suggest that its therapeutic targeting in specific subpopulations could lead to novel fibroblast-targeted therapies.

To address the question of whether the IFNg can be analyzed using primary tumor material (P-IFNg) instead of LN-IFNg or, in the case of incongruencies, has a higher predictive value when combined with LN-IFNg, we analyzed the IFNg signature in paired samples (P and LN) from stage III melanoma pts. Paraffin primary tumor tissue from pts with stage III melanoma, treated in the OpACIN-neo, PRADO and DONIMI trials (neoadjuvant anti-PD1 +/- anti-CTLA4 +/- domatinostat), was retrospectively analyzed with the nanostring nCounter PanCancer immune profiling panel and compared to fresh frozen LN biopsies. Our results suggest that pts with concurrently high IFNg-signature expressions (high IFNg in P and LN) have a better outcome than LN-IFNg high pts only. If confirmed, these findings could inform treatment selection and prognosis.

B16 cells subcutaneously exposed to TFP in mice induced an immune and inflammatory response to inhibit tumors. The study of the function of TFP-reeducated B16 cells to improve cancer immunotherapy may be of particular research interest. This approach could be an alternative and more efficient strategy to deliver cytokines and open up new possibilities for long-lasting, multi-level tumor control.

This tumor vaccine therapy may increase antigen exposure, synergistically activate the immune system, and ultimately improve remission rates. A vaccine strategy designed to induce effective tumor immune response is being considered for cancer immunotherapy.

In conclusion, our study highlights the critical role played by ISG20 within the network underlying cisplatin resistance in ovarian cancer. Targeting ISG20 using IFN-γ or TGF-β1 inhibitors may represent a promising therapeutic strategy for treating ovarian cancer.

In conclusion, we show that, upon exposure to patient-derived S. aureus and SE, keratinocytes stimulate IL-2Rγ/JAK3-dependent proliferation of malignant and non-malignant T-cells in an environment with non-malignant T-cells. These findings suggest that keratinocytes in the TME play a key role in S. aureus mediated disease activity in CTCL.

Our results showed that the inflammation and neuroinflammation in neurobrucellosis of striped dolphins mimic human neurobrucellosis and in vitro and in vivo studies in laboratory animals. Cetacean disease surveillance can be exploited to expand the knowledge of the pathogenesis and immunology of infectious diseases, particularly brucellosis, under a One Health approach.

Functionally, GBP1 was mainly expressed in macrophages and strongly correlated with chemokines involved in T-cell migration. Therefore, our study comprehensively investigated the potential role of GBP1 in immunotherapy, which could serve as a novel biomarker for immunotherapy and a target for drug development.

The target genes of upregulated exosomal miRNAs substantially contributed to the response to stimulus, metabolic pathways and PI3K-Akt signaling pathway. Our findings improve our understanding of the biological characteristics of hAECs after proinflammatory factor pretreatment and provide novel insights to strengthen and optimize the therapeutic potential of hAECs and their secretome in regenerative medicine.

mesenteroides existing enhances T cells viability and activity. GPCR41/42 is a possible link between L. mesenteroides, YAP-1 and PD-L1.