Neoantigen mRNA vaccines and A ₂ A receptor antagonism: A strategy to enhance T cell immunity

Human Vaccines & Immunotherapeutics, Journal Year: 2025, Volume and Issue: 21(1)

Published: Jan. 30, 2025

Although neo-antigen mRNA vaccines are promising for personalized cancer therapy, their effectiveness is often limited by the immunosuppressive tumor microenvironment (TME). The adenosine A2A receptor (A2AR) inhibits dendritic cell (DC) function and weakens antitumor T responses through hypoxia-driven mechanisms within TME. This review explores a novel strategy combining with A2AR antagonists (A2ARi). By targeting A2AR, this approach reduces TME-induced immunosuppression, enhances DC activation, improves presentation. also discusses lipid nanoparticles (LNPs) to co-deliver A2ARi vaccines, optimizing effectiveness. integration of mRNA-LNPs modulation offers overcome stimulate achieve precise anti-tumor minimal off-target effects. synergy represents significant progress in immunotherapy, advancing potential neoantigen therapies.

Language: Английский

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Purine metabolism-associated key genes depict the immune landscape in gout patients

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 17, 2025

Language: Английский

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Unveiling purine metabolism dysregulation orchestrated immunosuppression in advanced pancreatic cancer and concentrating on the central role of NT5E

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 1, 2025

The dismal efficacy of immunotherapy for Pancreatic cancer (PC) can be predominantly ascribed to its distinctive cold-tumor properties. by-products purine metabolic reprogramming are extensively engaged in tumor immune modulation, influencing the functions and recruitment cells molding an microenvironment that is propitious growth. We harnessed single-cell transcriptomics spatial concurrently analyze metabolism (PM) features PC microenvironment. quantitatively appraised PM traits diverse cell subsets via scoring algorithms such as AUCell Ucell. Moreover, development cell-cell interaction analysis elucidated alterations TME induced by dysregulation. Additionally, we defined disorder characteristics patients utilized this assess phenotypes prognoses patient population. Also, identified crucial intermediate genes impact establishment immunosuppressive environment within PC, validated them through sectioning co-culture experiments. Multi - dimensional transcriptome data unique heterogeneity microenvironment, which manifested fibroblasts demonstrating higher scores TME. Cellchat revealed malignant with elevated expression were concomitantly associated frequent interactions CAFs well high ligand-receptor pairs transcription factors. Spatial further corroborated finding. Furthermore, newly constructed criteria indicated levels a lack response Finally, study singular role NT5E immunosuppression resulting from PC. CCK8 invasion experiments following model demonstrated intervention targeting could reverse augmented malignancy co-cultured CAFs. potentially key target reversing "stiff-cancer" This demonstrates disorders impinge upon exacerbate engendered progression fibrosis. Therapeutic strategies or may offer ray hope advanced PDAC.

Language: Английский

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Ultrasound-Activatable Nanoprobes for Imaging-Guided Inhibition of Immunosuppressor Production in Tumor Microenvironment

ACS Applied Nano Materials, Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

Language: Английский

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Tumor Microenvironment Drives the Cross-Talk Between Co-Stimulatory and Inhibitory Molecules in Tumor-Infiltrating Lymphocytes: Implications for Optimizing Immunotherapy Outcomes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12848 - 12848

Published: Nov. 29, 2024

This review explores some of the complex mechanisms underlying antitumor T-cell response, with a specific focus on balance and cross-talk between selected co-stimulatory inhibitory pathways. The tumor microenvironment (TME) fosters both activation exhaustion, dual role influenced by local presence immune checkpoints (ICs), which are exploited cancer cells to evade surveillance. Recent advancements in IC blockade (ICB) therapies have transformed treatment. However, only fraction patients respond favorably, highlighting need for predictive biomarkers combination overcome ICB resistance. A crucial aspect is represented complexity TME, encompasses diverse cell types that either enhance or suppress responses. underscores importance identifying most critical molecules developing approaches tailored patient-specific molecular profiles maximize therapeutic efficacy inhibitors clinical outcomes.

Language: Английский

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Combined cancer immunotherapy based on targeting adenosine pathway and PD-1/PDL-1 axis

Expert Opinion on Therapeutic Targets, Journal Year: 2024, Volume and Issue: 28(9), P. 757 - 777

Published: Sept. 1, 2024

Cancer immunotherapy has revolutionized the field of oncology, offering new hope to patients with advanced malignancies. Tumor-induced immunosuppression limits effectiveness current immunotherapeutic strategies, such as PD-1/PDL-1 checkpoint inhibitors. Adenosine, a purine nucleoside molecule, is crucial this because it stops T cells from activating and helps regulatory grow. Targeting adenosine pathway blocking potential way boost immune system's response tumors.

Language: Английский

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