Intra-Tumoral Activation of Endosomal TLR Pathways Reveals a Distinct Role for TLR3 Agonist Dependent Type-1 Interferons in Shaping the Tumor Immune Microenvironment
| العنوان: | Intra-Tumoral Activation of Endosomal TLR Pathways Reveals a Distinct Role for TLR3 Agonist Dependent Type-1 Interferons in Shaping the Tumor Immune Microenvironment |
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| المؤلفون: | Kenneth G. Geles, Graham D. Thomas, Joseph Katakowski, Xiao Wang, Shobha Potluri, Shahram Salek-Ardakani, Purnima Sundar, Cecilia Oderup, Wenjing Yang, Luca Micci |
| المصدر: | Frontiers in Oncology Frontiers in Oncology, Vol 11 (2021) |
| بيانات النشر: | Frontiers Media S.A., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Agonist, Cancer Research, tumor, medicine.drug_class, medicine.medical_treatment, Antigen presentation, chemical and pharmacologic phenomena, IFN - interferon, 03 medical and health sciences, 0302 clinical medicine, Immune system, Cancer immunotherapy, Interferon, TLR9 agonist, medicine, TLR7 agonist, RC254-282, Original Research, Tumor microenvironment, Chemistry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, FOXP3, virus diseases, TLR - toll-like receptor, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, TLR3, scRNA-Seq, Cancer research, TLR3 agonist, medicine.drug |
| الوصف: | Toll-like receptor (TLR) agonists have received considerable attention as therapeutic targets for cancer immunotherapy owing to their ability to convert immunosuppressive tumor microenvironments towards a more T-cell inflamed phenotype. However, TLRs differ in their cell expression profiles and intracellular signaling pathways, raising the possibility that distinct TLRs differentially influence the tumor immune microenvironment. Using single-cell RNA-sequencing, we address this by comparing the tumor immune composition of B16F10 melanoma following treatment with agonists of TLR3, TLR7, and TLR9. Marked differences are observed between treatments, including decreased tumor-associated macrophages upon TLR7 agonist treatment. A biased type-1 interferon signature is elicited upon TLR3 agonist treatment as opposed to a type-2 interferon signature with TLR9 agonists. TLR3 stimulation was associated with increased macrophage antigen presentation gene expression and decreased expression of PD-L1 and the inhibitory receptors Pirb and Pilra on infiltrating monocytes. Furthermore, in contrast to TLR7 and TLR9 agonists, TLR3 stimulation ablated FoxP3 positive CD4 T cells and elicited a distinct CD8 T cell activation phenotype highlighting the potential for distinct synergies between TLR agonists and combination therapy agents. |
| اللغة: | English |
| تدمد: | 2234-943X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::26e9b85a57e72b54ecd687ee8abbd857 http://europepmc.org/articles/PMC8351420 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....26e9b85a57e72b54ecd687ee8abbd857 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2234943X |
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