PMC:6562565 / 33709-38654 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6562565","sourcedb":"PMC","sourceid":"6562565","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6562565","text":"Target Treatment Tumor model Outcome of adenosine axis blockade depends on presence/unhindered function of Impact on the TME\nCD73 ➣ mAbs:\nTY/23 (368, 378–384)\n2C5 IgG2a (384)\nOleclumab (385)\nAD2 (386)\n➣ Pharmacologic inhibitor:\nAPCP (378, 379, 381, 383, 384, 387–389) ➣ Breast:\n4T1.2 (368, 382, 383)\nE0771 (368)\nLM3a (386)\nMDA-MB-231a (386)\n➣ Melanoma:\nB16-SIY (378)\nB16-F10 (379, 381, 384, 387, 389)\nK1735 (381)\nLWT1 (384)\n➣ Ovarian:\nID8 (378, 388)\n➣ Prostate:\nTRAMP-C1 (380)\nRM-1 (382)\n➣ Colon:\nCT26 (385)\nMC38-OVA (382)\n➣ Fibrosarcoma: MCA-induced (380, 382)\n➣ Lymphoma:\nEG7 (379) ➣ Primary tumor expansionrate ↓ (368, 378–382, 385, 387, 389)\nHost CD73 (387)\nA2AR on hematopoietic cells (368)\nT cells, NK cells or B cells (368)\nT cells (381)\nCD8 T cells (380)\nIFN-γ (382)\nIL-17A (381)\nPartially retained inmice depleted of B cells (381)\nRetained in perforin KO mice (382)\n➣ Metastasis formation ↓ (368, 379, 380, 384, 386)\nRetained against tumor cells with significantly reduced CD73 (386)\nHost CD73 (380)\nMDSCs (384)\nRetained in mice depleted of T cells or NK cells (380)\nRetained in SCID mice lacking T cells, NK cells and functional B cells (386)\nHost FcRIV (384)\nFcR binding capacity (384)\nIndependent of the capacity to suppress CD73 catalytic activity (384, 386)\n➣ Survival↑ (378, 382, 384, 388) ↑ CD8+ T cells (381, 385, 389)↑ tumor-specific CD8+ T cells (382)↓ CD73 on CD4+/CD8+ T cells (382, 384)↑ B cells (381)↓ Tregs (389)↑ MDSCs (384)↓ CD73 on MDSCs (384)↑ IFN-γ, TNF-α, IL-17A (381)↓ Ki67+ cells (381)↓ Bcl-2+ cells (381)↓ Microvessel density (383)↓ VEGF (383)\nCD39 ➣ mAb:\n9-8B (390)\n➣ Pharmacologic inhibitor:\nPOM-1 (391) ➣ Melanoma: B16-F10 (391)\n➣ Colon: MCA38 (391)\n➣ Sarcoma: IGN-SRC- 004a (390) ➣ Primary tumor expansion rate ↓ (391)\nHost CD39 (391)\n➣ Survival ↑ (390)\nRetained in NOG mice lacking T cells, B cells, NK cells and functional macrophages (390)\nCD38 ➣ mAb:\nNIMR-5 (96)\n➣ Pharmacologic inhibitor:\nRhein (96) ➣ Lung:\n344SQ (96)\nLLC-JSP (96)\n531LN3 (96) ➣ Primary tumor expansion rate ↓ (96)\nCD8+ T cells (96) ↑ CD8+ T cells (96)↑ CD44hiCD62Llo CD8+ T cells (96)↓ PD-1+TIME3+ CD8+ T cells (96)↓ Tregs (96)↓ MDSCs (96)\nIntratumoral hypoxia Respiratory hyperoxia (60% O2) (9, 293) ➣ Breast: 4T1 (293)\n➣ Melanoma:\nB16 (9)\nB16-F10 (293)\nCL8-1 (9)\n➣ Fibrosarcoma: MCA205 (9, 293) ➣ Primary tumor expansion rate ↓ (9)\n➣ Metastasis formation ↓ (293)\nCD4 \u003e CD8 \u003e NK cells (293)\nHost A2AR (293)\nIndependent of 60%O2-induced ROS production (293)\n➣ Survival ↑ (9, 293) ↓ Hypoxia (9, 293)↓ HIF- 1α (9)↑ FHL-1, FIH-1, VHL (HIF- 1α inhibitors) (9)↓ CD39, CD73, A2AR, A2BR, COX-2 mRNA (9)↓ extracellular adenosine (9)↑ CD8+, CD69+, CD44+ cells (293)↓ Tregs (293)↑ IL-2, IL-12, CXCL9, CXCL10, CXCL11 mRNA (293)↓ TGF-β (293)↓ FOXP3 in Tregs (293)↓ CD39, CD73, CTLA-4 on Tregs (293)↑ MHC class I on tumor cells (9)↓ VEGF, VEGF mRNA (9)↓ Microvessel density (9)\nA2AR ➣ Antagonists:\nZM241385 (38, 54)\nZM241365 (389)\nSCH58261 (54, 292, 384, 392–394)\nFSPTP (395)\nCPI-444 (396)\nPBF-509 (397) ➣ Breast:\n4T1.2 (292)\n➣ Melanoma:\nB16-F10 (292, 384, 389, 394, 395, 397)\nCL8-1 (38)\nBRAFV600E-PTEN-deficient mice (393)\nLWT1 (393)\n➣ Colon:\nCT26 (396)\nMC38 (396)\n➣ NSCLC: PC9a (54)\n➣ Bladder: MB49 (395)\n➣ HNSCC: Tgfbr1/Pten double KO (392)\n➣ Fibrosarcoma: MCA205 (397) ➣ Primary tumor expansion rate ↓ (38, 54, 389, 392, 393, 396)\nT cells (38)\nRetained in NUDE micelackingT cells (54)\n➣ Metastasis formation ↓ (292, 384, 393, 394, 397)\nTumor CD73 (292, 394)\nHost A2AR (292)\nT cells, B cells or NK cells (292)\nPerforin (292)\n➣ Survival↑ (384, 396)\nCD8 T cells \u003e NK cells (394) ↓ CD8+, CD4+ T cells (395)↑ CD8+ T cells (389, 392, 393)↑ CD69 on CD8+ T cells (393)↓ A2AR+ CD8+ T cells (392)↑ IFN-γ+ CD8+ T cells (392)↑ T-bet, 41-BB in/on CD44+CD8+ T cells (396)↑ IFN-γ, TNF-α production by CD8+ T cells (392)↑ stimulation-induced IFN-γ/TNF-αproduction by CD8+ T cells (396)↑ NK cells (393, 395)↑ GzB+ NK cells (292)↓ Tregs (389, 392, 393)↓ PD-1, LAG3, FOXP3 on Tregs (396)↓ A2AR+ Tregs (392)↓ FOXP3 (392)\nA2BR ➣ Antagonists:\nPSB1115 (292, 315, 359, 398)\nATL-801 (399) ➣ Breast:\n4T1.2 (292, 359, 368, 399)\nE0771 (359)\n➣ Melanoma:\nB16-F10 (292, 315, 359, 398)\nLWT1 (359)\n➣ Bladder: MB49 (399) ➣ Primary tumor expansion rate ↓ (315, 398, 399)\nMature T cells (399)\nT cells (398)\nHost A2BR (399)\nHost CXCR3 (399)\nRetained in A2AR−/− mice (399)\nRetained in mice depleted of MDSCs but lost upon adoptive transfer of MDSCs (398)\n➣ Metastasis formation ↓ (292, 359, 368)\nTumor CD73 (292)\nRetained in RAG−/−cγ−/− mice lacking T cells, B cells and NK cells (292)\nRetained in mice depleted of T cells, NK cells D11c+ DCs or macrophages (359)\n➣ Survival↑ (359)\nTumor A2BR (359)\nRetained in mice depleted of T cells or NK cells (359) ↑ CD8+ T cells (315, 398)↑ CXCR3+ T cells (399)↑ NKT cells (315, 398)↓ MDSCs (315, 398)↑IFN-γ, CXCL10 mRNA (399)↑ IFN-γ, TNF-α, GzB (398)↓ MCP-1, IL-10 (398)↓ VEGF (315)↓ Microvessel density 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