Dysregulated metabolism: A friend-to-foe skewer of macrophages

References

• Cassetta L, Fragkogianni S, Sims AH, et al. Human tumor-associated macrophage and monocyte transcriptional landscapes reveal cancer-specific reprogramming, biomarkers, and therapeutic targets. Cancer Cell. 2019;35(4):588–602. e10. doi:10.1016/j.ccell.2019.02.009.
   PubMed Web of Science ®Google Scholar
• Xiang X, Wang J, Lu D, et al. Targeting tumor-associated macrophages to synergize tumor immunotherapy. Sig Transduct Target Ther. 2021;6(1):1–12. doi:10.1038/s41392-021-00484-9.
   PubMed Web of Science ®Google Scholar
• Kamerkar S, Leng C, Burenkova O, et al. Exosome-mediated genetic reprogramming of tumor-associated macrophages by exoASO-STAT6 leads to potent monotherapy antitumor activity. Sci Adv. 2022;8(7):eabj7002. doi:10.1126/sciadv.abj7002.
   PubMed Web of Science ®Google Scholar
• Di Mitri D, Mirenda M, Vasilevska J, et al. Re-education of tumor-associated macrophages by CXCR2 blockade drives senescence and tumor inhibition in advanced prostate cancer. Cell Rep. 2019;28(8):2156–2168. e5. doi:10.1016/j.celrep.2019.07.068.
   PubMed Web of Science ®Google Scholar
• Sarode P, Zheng X, Giotopoulou GA, et al. Reprogramming of tumor-associated macrophages by targeting β-catenin/FOSL2/ARID5A signaling: A potential treatment of lung cancer. Sci Adv. 2020;6(23):eaaz6105. doi:10.1126/sciadv.aaz6105.
   PubMed Web of Science ®Google Scholar
• Bronte V. Deciphering macrophage and monocyte code to stratify human breast cancer patients. Cancer Cell. 2019;35(4):538–539. doi:10.1016/j.ccell.2019.03.010.
   PubMed Web of Science ®Google Scholar
• Mortezaee K, Majidpoor J. Roles for macrophage-polarizing interleukins in cancer immunity and immunotherapy. Cell Oncol. 2022;45(3):333–353. doi:10.1007/s13402-022-00667-8.
   Web of Science ®Google Scholar
• Ries CH, Cannarile MA, Hoves S, et al. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell. 2014;25(6):846–859. doi:10.1016/j.ccr.2014.05.016.
   PubMed Web of Science ®Google Scholar
• Kumar V, Donthireddy L, Marvel D, et al. Cancer-associated fibroblasts neutralize the anti-tumor effect of CSF1 receptor blockade by inducing PMN-MDSC infiltration of tumors. Cancer Cell. 2017;32(5):654–668. e5. doi:10.1016/j.ccell.2017.10.005.
   PubMed Web of Science ®Google Scholar
• Chen D, Xie J, Fiskesund R, et al. Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype. Nat Commun. 2018;9(1):1–15. doi:10.1038/s41467-018-04169-w.
   PubMedGoogle Scholar
• Hu G, Su Y, Kang BH, et al. High-throughput phenotypic screen and transcriptional analysis identify new compounds and targets for macrophage reprogramming. Nat Commun. 2021;12(1):1–14. doi:10.1038/s41467-021-21066-x.
   PubMed Web of Science ®Google Scholar
• Xu H, Li D, Ma J, et al. The IL-33/ST2 axis affects tumor growth by regulating mitophagy in macrophages and reprogramming their polarization. Cancer Biol Med. 2021;18(1):172–183. doi:10.20892/j.issn.2095-3941.2020.0211.
   PubMed Web of Science ®Google Scholar
• Su S, Liu Q, Chen J, et al. A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell. 2014;25(5):605–620. doi:10.1016/j.ccr.2014.03.021.
   PubMed Web of Science ®Google Scholar
• Georgoudaki A-M, Prokopec KE, Boura VF, et al. Reprogramming tumor-associated macrophages by antibody targeting inhibits cancer progression and metastasis. Cell Rep. 2016;15(9):2000–2011. doi:10.1016/j.celrep.2016.04.084.
   PubMed Web of Science ®Google Scholar
• Mills E, Kelly B, Logan A, et al. Repurposing mitochondria from ATP production to ROS generation drives a pro-inflammatory phenotype in macrophages that depends on succinate oxidation by complex II. Cell. 2016;167(2):457–470.e13. doi:10.1016/j.cell.2016.08.064.
   PubMed Web of Science ®Google Scholar
• Yuan Q, Gu J, Zhang J, et al. MyD88 in myofibroblasts enhances colitis-associated tumorigenesis via promoting macrophage M2 polarization. Cell Rep. 2021;34(5):108724. doi:10.1016/j.celrep.2021.108724.
   PubMed Web of Science ®Google Scholar
• Mortezaee K. Normalization in tumor ecosystem: opportunities and challenges. Cell Biol Int. 2021;45(10):2017–2030. doi:10.1002/cbin.11655.
   PubMed Web of Science ®Google Scholar
• Klug F, Prakash H, Huber PE, et al. Low-dose irradiation programs macrophage differentiation to an iNOS+/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell. 2013;24(5):589–602. doi:10.1016/j.ccr.2013.09.014.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Yu Z, Ma R, et al. lncRNA-Xist/miR-101-3p/KLF6/C/EBPα axis promotes TAM polarization to regulate cancer cell proliferation and migration. Mol Ther Nucleic Acids. 2021;23:536–551. doi:10.1016/j.omtn.2020.12.005.
   PubMedGoogle Scholar
• Ochocka N, Segit P, Walentynowicz KA, et al. Single-cell RNA sequencing reveals functional heterogeneity of glioma-associated brain macrophages. Nat Commun. 2021;12(1):1–14. doi:10.1038/s41467-021-21407-w.
   PubMed Web of Science ®Google Scholar
• Yang Q, Zhang H, Wei T, et al. Single-Cell RNA sequencing reveals the heterogeneity of tumor-associated macrophage in non-small cell lung cancer and differences between sexes. Front Immunol. 2021;12:756722. doi:10.3389/fimmu.2021.756722.
   PubMed Web of Science ®Google Scholar
• Bachy S, Wu Z, Gamradt P, et al. βig-h3-structured collagen alters macrophage phenotype and function in pancreatic cancer. Iscience. 2022;25(2):103758. doi:10.1016/j.isci.2022.103758.
   PubMed Web of Science ®Google Scholar
• Kubala MH, Punj V, Placencio-Hickok VR, et al. Plasminogen activator inhibitor-1 promotes the recruitment and polarization of macrophages in cancer. Cell Rep. 2018;25(8):2177–2191. e7. doi:10.1016/j.celrep.2018.10.082.
   PubMed Web of Science ®Google Scholar
• Kovaleva OV, Samoilova DV, Shitova MS, et al. Tumor associated macrophages in kidney cancer. Anal Cell Pathol. 2016;2016:1–6. doi:10.1155/2016/9307549.
   Web of Science ®Google Scholar
• Sun Y, Xu S. Tumor-associated CD204-positive macrophage is a prognostic marker in clinical stage I lung adenocarcinoma. Biomed Res Int. 2018;2018:1–7. doi:10.1155/2018/8459193.
   Web of Science ®Google Scholar
• Farmaki E, Kaza V, Chatzistamou I, et al. CCL8 promotes postpartum breast cancer by recruiting M2 macrophages. Iscience. 2020;23(6):101217. doi:10.1016/j.isci.2020.101217.
   PubMed Web of Science ®Google Scholar
• Hamm A, Prenen H, Van Delm W, et al. Tumour-educated circulating monocytes are powerful candidate biomarkers for diagnosis and disease follow-up of colorectal cancer. Gut. 2016;65(6):990–1000. doi:10.1136/gutjnl-2014-308988.
   PubMed Web of Science ®Google Scholar
• Mortezaee K, Majidpoor J. CD8+ T Cells in SARS-CoV-2 induced disease and cancer-clinical perspectives. Front Immunol. 2022;13:864298–864298. doi:10.3389/fimmu.2022.864298.
   PubMed Web of Science ®Google Scholar
• Chiocca EA, Yu JS, Lukas RV, et al. Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial. Sci Transl Med. 2019;11(505):eaaw5680. doi:10.1126/scitranslmed.aaw5680.
   PubMed Web of Science ®Google Scholar
• Kirchhammer N, Trefny MP, Natoli M, et al. Successful IL-12 cancer immunotherapy requires NK cell-derived CCL5 for anti-tumor DC-T cell crosstalk. bioRxiv. 2021;
   Google Scholar
• Togashi Y, Shitara K, Nishikawa H. Regulatory T cells in cancer immunosuppression—implications for anticancer therapy. Nat Rev Clin Oncol. 2019;16(6):356–371. doi:10.1038/s41571-019-0175-7.
   PubMed Web of Science ®Google Scholar
• Chu Z, Gu L, Hu Y, et al. STAG2 regulates interferon signaling in melanoma via enhancer loop reprogramming. Nat Commun. 2022;13(1):1–11. doi:10.1038/s41467-022-29541-9.
   PubMed Web of Science ®Google Scholar
• Benci JL, Johnson LR, Choa R, et al. Opposing functions of interferon coordinate adaptive and innate immune responses to cancer immune checkpoint blockade. Cell. 2019;178(4):933–948. e14. doi:10.1016/j.cell.2019.07.019.
   PubMed Web of Science ®Google Scholar
• Vilsmaier T, Rack B, König A, SUCCESS Study Group, et al. Influence of circulating tumour cells on production of IL-1α, IL-1β and IL-12 in sera of patients with primary diagnosis of breast cancer before treatment. Anticancer Res. 2016;36(10):5227–5236. doi:10.21873/anticanres.11093.
   PubMed Web of Science ®Google Scholar
• Majidpoor J, Mortezaee K. Interleukin-2 therapy of cancer-clinical perspectives. Int Immunopharmacol. 2021;98:107836. doi:10.1016/j.intimp.2021.107836.
   PubMedGoogle Scholar
• Mortezaee K, Najafi M. Immune system in cancer radiotherapy: resistance mechanisms and therapy perspectives. Crit. Rev Oncol/Hematol. 2021;157:103180. doi:10.1016/j.critrevonc.2020.103180.
   PubMed Web of Science ®Google Scholar
• La Fleur L, Botling J, He F, et al. Targeting MARCO and IL37R on immunosuppressive macrophages in lung cancer blocks regulatory T cells and supports cytotoxic lymphocyte function. Cancer Res. 2021;81(4):956–967. doi:10.1158/0008-5472.CAN-20-1885.
   PubMed Web of Science ®Google Scholar
• Kwak T, Wang F, Deng H, et al. Distinct populations of immune-suppressive macrophages differentiate from monocytic myeloid-derived suppressor cells in cancer. Cell Rep. 2020;33(13):108571. doi:10.1016/j.celrep.2020.108571.
   PubMed Web of Science ®Google Scholar
• Mortezaee K. Myeloid-derived suppressor cells in cancer immunotherapy-clinical perspectives. Life Sci. 2021;277:119627. doi:10.1016/j.lfs.2021.119627.
   PubMed Web of Science ®Google Scholar
• Farhood B, Najafi M, Salehi E, et al. Disruption of the redox balance with either oxidative or anti-oxidative overloading as a promising target for cancer therapy. J Cell Biochem. 2019;120(1):71–76. doi:10.1002/jcb.27594.
   PubMed Web of Science ®Google Scholar
• Mortezaee K, Najafi M, Farhood B, et al. Resveratrol as an adjuvant for normal tissues protection and tumor sensitization. Curr Cancer Drug Targets. 2020;20(2):130–145. doi:10.2174/1568009619666191019143539.
   PubMed Web of Science ®Google Scholar
• Yang C, Dou R, Wei C, et al. Tumor-Derived Exosomal MicroRNA-106b-5p Activates the Interaction between EMT-Cancer Cells and M2-Subtype TAMs to Facilitate Colorectal Cancer Metastasis. Mol Ther J Am Soc Gene Ther. 2021;29(6):2088–2107. doi:10.1016/j.ymthe.2021.02.006.
   PubMed Web of Science ®Google Scholar
• Linde N, Casanova-Acebes M, Sosa MS, et al. Macrophages orchestrate breast cancer early dissemination and metastasis. Nat Commun. 2018;9(1):1–14. doi:10.1038/s41467-017-02481-5.
   PubMedGoogle Scholar
• Mortezaee K. Enriched cancer stem cells, dense stroma, and cold immunity: Interrelated events in pancreatic cancer. J Biochem Mol Toxicol. 2021;35(4):e22708. doi:10.1002/jbt.22708.
   PubMed Web of Science ®Google Scholar
• Yin J, Kim SS, Choi E, et al. ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages. Nat Commun. 2020;11(1):1–15. doi:10.1038/s41467-020-16789-2.
   PubMed Web of Science ®Google Scholar
• Mortezaee K. Organ tropism in solid tumor metastasis: an updated review. Future Oncol. 2021;17(15):1943–1961. doi:10.2217/fon-2020-1103.
   PubMed Web of Science ®Google Scholar
• Najafi M, Mortezaee K, Majidpoor J. Stromal reprogramming: a target for tumor therapy. Life Sci. 2019;239:117049.
   PubMed Web of Science ®Google Scholar
• Nakamura Y, Kinoshita J, Yamaguchi T, et al. Crosstalk between cancer-associated fibroblasts and immune cells in peritoneal metastasis: inhibition in the migration of M2 macrophages and mast cells by Tranilast. Gastric Cancer. 2022;25(3):515–526. doi:10.1007/s10120-021-01275-5.
   PubMed Web of Science ®Google Scholar
• Takahashi H, Sakakura K, Kudo T, et al. Cancer-associated fibroblasts promote an immunosuppressive microenvironment through the induction and accumulation of protumoral macrophages. Oncotarget. 2017;8(5):8633–8647. doi:10.18632/oncotarget.14374.
   PubMedGoogle Scholar
• Comito G, Giannoni E, Segura C, et al. Cancer-associated fibroblasts and M2-polarized macrophages synergize during prostate carcinoma progression. Oncogene. 2014;33(19):2423–2431. doi:10.1038/onc.2013.191.
   PubMed Web of Science ®Google Scholar
• Palsson-McDermott EM, Curtis AM, Goel G, et al. Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the warburg effect in LPS-activated macrophages. Cell Metab. 2015;21(1):65–80. doi:10.1016/j.cmet.2014.12.005.
   PubMed Web of Science ®Google Scholar
• Jiang B. Aerobic glycolysis and high level of lactate in cancer metabolism and microenvironment. Genes Dis. 2017;4(1):25–27. doi:10.1016/j.gendis.2017.02.003.
   PubMed Web of Science ®Google Scholar
• Yan K, Da T-T, Bian Z-H, et al. Multi-omics analysis identifies FoxO1 as a regulator of macrophage function through metabolic reprogramming. Cell Death Dis. 2020;11(9):1–14. doi:10.1038/s41419-020-02982-0.
   PubMed Web of Science ®Google Scholar
• Dowling JK, Afzal R, Gearing LJ, et al. Mitochondrial arginase-2 is essential for IL-10 metabolic reprogramming of inflammatory macrophages. Nat Commun. 2021;12(1):1–14. doi:10.1038/s41467-021-21617-2.
   PubMed Web of Science ®Google Scholar
• Wang F, Zhang S, Jeon R, et al. Interferon gamma induces reversible metabolic reprogramming of M1 macrophages to sustain cell viability and pro-inflammatory activity. EBioMed. 2018;30:303–316. doi:10.1016/j.ebiom.2018.02.009.
   PubMed Web of Science ®Google Scholar
• Huang SC-C, Everts B, Ivanova Y, et al. Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nat Immunol. 2014;15(9):846–855. doi:10.1038/ni.2956.
   PubMed Web of Science ®Google Scholar
• Wang F, Zhang S, Vuckovic I, et al. Glycolytic stimulation is not a requirement for M2 macrophage differentiation. Cell Metab. 2018;28(3):463–475. e4. doi:10.1016/j.cmet.2018.08.012.
   PubMed Web of Science ®Google Scholar
• Jha AK, Huang SC-C, Sergushichev A, et al. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity. 2015;42(3):419–430. doi:10.1016/j.immuni.2015.02.005.
   PubMed Web of Science ®Google Scholar
• Mortezaee K. Redox tolerance and metabolic reprogramming in solid tumors. Cell Biol Int. 2021;45(2):273–286. doi:10.1002/cbin.11506.
   PubMed Web of Science ®Google Scholar
• Bouchard A, Collin B, Garrido C, et al. GARP: A Key Target to Evaluate Tumor Immunosuppressive Microenvironment. Biology. 2021;10(9):836. doi:10.3390/biology10090836.
   PubMedGoogle Scholar
• Jin H, Sun L, Tang L, et al. Expression of GARP is increased in tumor-infiltrating regulatory T cells and is correlated to clinicopathology of lung cancer patients. Front Immunol. 2017;8:138.
   PubMed Web of Science ®Google Scholar
• Zhang M, Pan X, Fujiwara K, et al. Pancreatic cancer cells render tumor-associated macrophages metabolically reprogrammed by a GARP and DNA methylation-mediated mechanism. Sig Transduct Target Ther. 2021;6(1):1–18. doi:10.1038/s41392-021-00769-z.
   PubMed Web of Science ®Google Scholar
• Wenes M, Shang M, Matteo MD, et al. Macrophage metabolism controls tumor blood vessel morphogenesis and metastasis. Cell Metab. 2016;24(5):701–715. doi:10.1016/j.cmet.2016.09.008.
   PubMed Web of Science ®Google Scholar
• He K, Jia S, Lou Y, et al. Cryo-thermal therapy induces macrophage polarization for durable anti-tumor immunity. Cell Death Dis. 2019;10(3):1–16. doi:10.1038/s41419-019-1459-7.
   Google Scholar
• Tannahill G, Curtis A, Adamik J, et al. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature. 2013;496(7444):238–242. doi:10.1038/nature11986.
   PubMed Web of Science ®Google Scholar
• Eissmann MF, Dijkstra C, Jarnicki A, et al. IL-33-mediated mast cell activation promotes gastric cancer through macrophage mobilization. Nat Commun. 2019;10(1):1–16. doi:10.1038/s41467-019-10676-1.
   PubMedGoogle Scholar
• Raines LN, Zhao H, Wang Y, et al. PERK is a critical metabolic hub for immunosuppressive function in macrophages. Nat Immunol. 2022;23:431–445.
   PubMed Web of Science ®Google Scholar
• Majidpoor J, Mortezaee K. Interleukin-6 in SARS-CoV-2 induced disease: Interactions and therapeutic applications. Biomed Pharmacother. 2022;145:112419. doi:10.1016/j.biopha.2021.112419.
   PubMed Web of Science ®Google Scholar
• Paolini L, Adam C, Beauvillain C, et al. Lactic acidosis together with GM-CSF and M-CSF induces human macrophages toward an inflammatory protumor phenotype. Cancer Immunol Res. 2020;8(3):383–395. doi:10.1158/2326-6066.CIR-18-0749.
   PubMed Web of Science ®Google Scholar
• Bieniasz-Krzywiec P, Martín-Pérez R, Ehling M, et al. Podoplanin-expressing macrophages promote lymphangiogenesis and lymphoinvasion in breast cancer. Cell Metab. 2019;30(5):917–936. e10. doi:10.1016/j.cmet.2019.07.015.
   PubMed Web of Science ®Google Scholar
• Niu X, Ma J, Li J, et al. Sodium/glucose cotransporter 1-dependent metabolic alterations induce tamoxifen resistance in breast cancer by promoting macrophage M2 polarization. Cell Death Dis. 2021;12(6):1–15. doi:10.1038/s41419-021-03781-x.
   PubMed Web of Science ®Google Scholar
• El-Kenawi A, Gatenbee C, Robertson-Tessi M, et al. Acidity promotes tumour progression by altering macrophage phenotype in prostate cancer. Br J Cancer. 2019;121(7):556–566. doi:10.1038/s41416-019-0542-2.
   PubMed Web of Science ®Google Scholar
• de la Cruz-López KG, Castro-Muñoz LJ, Reyes-Hernández DO, et al. Lactate in the regulation of tumor microenvironment and therapeutic approaches. Front Oncol. 2019;9:1143.
   PubMed Web of Science ®Google Scholar
• LaMonte G, Tang X, Chen JL-Y, et al. Acidosis induces reprogramming of cellular metabolism to mitigate oxidative stress. Cancer Metab. 2013;1(1):23. doi:10.1186/2049-3002-1-23.
   PubMedGoogle Scholar
• Bohn T, Rapp S, Luther N, et al. Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages. Nat Immunol. 2018;19(12):1319–1329. doi:10.1038/s41590-018-0226-8.
   PubMed Web of Science ®Google Scholar
• Kratochvill F, Neale G, Haverkamp JM, et al. TNF counterbalances the emergence of M2 tumor macrophages. Cell Rep. 2015;12(11):1902–1914. doi:10.1016/j.celrep.2015.08.033.
   PubMed Web of Science ®Google Scholar
• Mortezaee K, Majidpoor J. Key promoters of tumor hallmarks. Int J Clin Oncol. 2022;27(1):45–58. doi:10.1007/s10147-021-02074-9.
   PubMed Web of Science ®Google Scholar
• Mortezaee K. Hypoxia induces core-to-edge transition of progressive tumoral cells: A critical review on differential yet corroborative roles for HIF-1α and HIF-2α. Life Sci. 2020;242:117145.
   PubMed Web of Science ®Google Scholar
• Laoui D, Van Overmeire E, Conza GD, et al. Tumor hypoxia does not drive differentiation of tumor-associated macrophages but rather fine-tunes the M2-like macrophage population. Cancer Res. 2014;74(1):24–30. doi:10.1158/0008-5472.CAN-13-1196.
   PubMed Web of Science ®Google Scholar
• Mortezaee K, Majidpoor J. (Im) maturity in Tumor Ecosystem. Front Oncol. 2021;11:813897–813897. doi:10.3389/fonc.2021.813897.
   PubMed Web of Science ®Google Scholar
• Geeraerts X, Fernández-Garcia J, Hartmann FJ, et al. Macrophages are metabolically heterogeneous within the tumor microenvironment. Cell Rep. 2021;37(13):110171. doi:10.1016/j.celrep.2021.110171.
   PubMed Web of Science ®Google Scholar
• Runtsch MC, Angiari S, Hooftman A, et al. Itaconate and itaconate derivatives target JAK1 to suppress alternative activation of macrophages. Cell Metab. 2022;34(3):487–501. e8. doi:10.1016/j.cmet.2022.02.002.
   PubMed Web of Science ®Google Scholar
• Mortezaee K, Majidpoor J. The impact of hypoxia on immune state in cancer. Life Sci. 2021;286:120057. doi:10.1016/j.lfs.2021.120057.
   PubMed Web of Science ®Google Scholar
• Palmieri EM, Menga A, Martín-Pérez R, et al. Pharmacologic or genetic targeting of glutamine synthetase skews macrophages toward an M1-like phenotype and inhibits tumor metastasis. Cell Rep. 2017;20(7):1654–1666. doi:10.1016/j.celrep.2017.07.054.
   PubMed Web of Science ®Google Scholar
• Jiang H, Wei H, Wang H, et al. Zeb1-induced metabolic reprogramming of glycolysis is essential for macrophage polarization in breast cancer. Cell Death Dis. 2022;13(3):1–14. doi:10.1038/s41419-022-04632-z.
   Web of Science ®Google Scholar
• Mortezaee K. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and liver fibrosis: A review. Cell Biochem Funct. 2018;36(6):292–302. doi:10.1002/cbf.3351.
   PubMed Web of Science ®Google Scholar
• Mortezaee K, Goradel NH, Amini P, et al. NADPH oxidase as a target for modulation of radiation response; implications to carcinogenesis and radiotherapy. Curr Mol Pharmacol. 2019;12(1):50–60. doi:10.2174/1874467211666181010154709.
   PubMed Web of Science ®Google Scholar
• Majidpoor J, Mortezaee K. Steps in metastasis: an updated review. Med Oncol. 2021;38(1):3–17. doi:10.1007/s12032-020-01447-w.
   PubMed Web of Science ®Google Scholar
• Anastasiou D, Poulogiannis G, Asara JM, et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science. 2011;334(6060):1278–1283. doi:10.1126/science.1211485.
   PubMed Web of Science ®Google Scholar
• Wang C, Zhang S, Liu J, et al. Secreted pyruvate kinase M2 promotes lung cancer metastasis through activating the integrin Beta1/FAK signaling pathway. Cell Rep. 2020;30(6):1780–1797. e6. doi:10.1016/j.celrep.2020.01.037.
   PubMed Web of Science ®Google Scholar
• Luo W, Hu H, Chang R, et al. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell. 2011;145(5):732–744. doi:10.1016/j.cell.2011.03.054.
   PubMed Web of Science ®Google Scholar
• Li L, Peng G, Liu X, et al. Pyruvate Kinase M2 Coordinates Metabolism Switch between Glycolysis and Glutaminolysis in Cancer Cells. Iscience. 2020;23(11):101684. doi:10.1016/j.isci.2020.101684.
   PubMed Web of Science ®Google Scholar
• Rolny C, Mazzone M, Tugues S, et al. HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF. Cancer Cell. 2011;19(1):31–44. doi:10.1016/j.ccr.2010.11.009.
   PubMed Web of Science ®Google Scholar
• Colegio OR, Chu N-Q, Szabo AL, et al. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature. 2014;513(7519):559–563. doi:10.1038/nature13490.
   PubMed Web of Science ®Google Scholar
• Majidpoor J, Mortezaee K. Angiogenesis as a hallmark of solid tumors-clinical perspectives. Cell Oncol. 2021;44(4):715–723. doi:10.1007/s13402-021-00602-3.
   PubMed Web of Science ®Google Scholar
• Ma R, Chu X, Jiang Y, et al. Pigment epithelium-derived factor, an anti-VEGF factor, delays ovarian cancer progression by alleviating polarization of tumor-associated macrophages. Cancer Gene Ther. 2022;:1–10. doi:10.1038/s41417-022-00447-4.
   Web of Science ®Google Scholar
• Pickert G, Lim HY, Weigert A, et al. Inhibition of GTP cyclohydrolase attenuates tumor growth by reducing angiogenesis and M2-like polarization of tumor associated macrophages. Int J Cancer. 2013;132(3):591–604. doi:10.1002/ijc.27706.
   PubMed Web of Science ®Google Scholar
• Casazza A, Laoui D, Wenes M, et al. Impeding macrophage entry into hypoxic tumor areas by Sema3A/Nrp1 signaling blockade inhibits angiogenesis and restores antitumor immunity. Cancer Cell. 2013;24(6):695–709. doi:10.1016/j.ccr.2013.11.007.
   PubMed Web of Science ®Google Scholar
• Cheng S-C, Quintin J, Cramer RA, et al. mTOR-and HIF-1α–mediated aerobic glycolysis as metabolic basis for trained immunity. Science. 2014;345(6204):1250684. doi:10.1126/science.1250684.
   PubMed Web of Science ®Google Scholar
• Sung Y-C, Jin P-R, Chu L-A, et al. Delivery of nitric oxide with a nanocarrier promotes tumour vessel normalization and potentiates anti-cancer therapies. Nat Nanotechnol. 2019;14(12):1160–1169. doi:10.1038/s41565-019-0570-3.
   PubMed Web of Science ®Google Scholar
• Mpekris F, Voutouri C, Baish JW, et al. Combining microenvironment normalization strategies to improve cancer immunotherapy. Proc Natl Acad Sci U S A. 2020;117(7):3728–3737. doi:10.1073/pnas.1919764117.
   PubMed Web of Science ®Google Scholar
• Mazzone M, Dettori D, de Oliveira RL, et al. Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization. Cell. 2009;136(5):839–851. doi:10.1016/j.cell.2009.01.020.
   PubMed Web of Science ®Google Scholar
• de Oliveira RL, Deschoemaeker S, Henze A-T, et al. Gene-targeting of Phd2 improves tumor response to chemotherapy and prevents side-toxicity. Cancer Cell. 2012;22(2):263–277. doi:10.1016/j.ccr.2012.06.028.
   PubMed Web of Science ®Google Scholar
• Zhu Y, Knolhoff BL, Meyer MA, et al. CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models. Cancer Res. 2014;74(18):5057–5069. doi:10.1158/0008-5472.CAN-13-3723.
   PubMed Web of Science ®Google Scholar
• Salvagno C, Ciampricotti M, Tuit S, et al. Therapeutic targeting of macrophages enhances chemotherapy efficacy by unleashing type I interferon response. Nat Cell Biol. 2019;21(4):511–521. doi:10.1038/s41556-019-0298-1.
   PubMed Web of Science ®Google Scholar
• Garris C, Pittet MJ. Therapeutically reeducating macrophages to treat GBM. Nat Med. 2013;19(10):1207–1208. doi:10.1038/nm.3355.
   PubMed Web of Science ®Google Scholar
• Pyonteck SM, Akkari L, Schuhmacher AJ, et al. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med. 2013;19(10):1264–1272. doi:10.1038/nm.3337.
   PubMed Web of Science ®Google Scholar
• Zhu Y, Yang J, Xu D, et al. Disruption of tumour-associated macrophage trafficking by the osteopontin-induced colony-stimulating factor-1 signalling sensitises hepatocellular carcinoma to anti-PD-L1 blockade. Gut. 2019;68(9):1653–1666. doi:10.1136/gutjnl-2019-318419.
   PubMed Web of Science ®Google Scholar
• Mortezaee K, Majidpoor J. Checkpoint inhibitor/interleukin-based combination therapy of cancer. Cancer Med. 2022; doi:10.1002/cam4.4659.
   PubMed Web of Science ®Google Scholar
• Majidpoor J, Mortezaee K. The efficacy of PD-1/PD-L1 blockade in cold cancers and future perspectives. Clinical Immunol. 2021;226:108707. doi:10.1016/j.clim.2021.108707.
   PubMed Web of Science ®Google Scholar
• Renner K, Bruss C, Schnell A, et al. Restricting glycolysis preserves T cell effector functions and augments checkpoint therapy. Cell Rep. 2019;29(1):135–150. e9. doi:10.1016/j.celrep.2019.08.068.
   PubMed Web of Science ®Google Scholar
• Kumar A, Chamoto K. Immune metabolism in PD-1 blockade-based cancer immunotherapy. Int Immunol. 2021;33(1):17–26. doi:10.1093/intimm/dxaa046.
   PubMed Web of Science ®Google Scholar
• Morrissey SM, Zhang F, Ding C, et al. Tumor-derived exosomes drive immunosuppressive macrophages in a pre-metastatic niche through glycolytic dominant metabolic reprogramming. Cell Metab. 2021;33(10):2040–2058. e10. doi:10.1016/j.cmet.2021.09.002.
   PubMed Web of Science ®Google Scholar
• Seifali E, Hassanzadeh G, Mahdavipour M, et al. Extracellular vesicles derived from human umbilical cord perivascular cells improve functional recovery in brain ischemic rat via the inhibition of apoptosis. Iran Biomed J. 2020;24(6):347.
   PubMedGoogle Scholar
• Wang X, Ding H, Li Z, et al. Exploration and functionalization of M1-macrophage extracellular vesicles for effective accumulation in glioblastoma and strong synergistic therapeutic effects. Sig Transduct Target Ther. 2022;7(1):1–16. doi:10.1038/s41392-022-00894-3.
   PubMed Web of Science ®Google Scholar
• Jiang H, Zhou L, Shen N, et al. M1 macrophage-derived exosomes and their key molecule lncRNA HOTTIP suppress head and neck squamous cell carcinoma progression by upregulating the TLR5/NF-κB pathway. Cell Death Dis. 2022;13(2):1–15. doi:10.1038/s41419-022-04640-z.
   Web of Science ®Google Scholar
• Najafi M, Majidpoor J, Toolee H, et al. The current knowledge concerning solid cancer and therapy. J Biochem Mol Toxicol. 2021;35(11):e22900. doi:10.1002/jbt.22900.
   PubMed Web of Science ®Google Scholar
• Sancho-Albero M, Rubio-Ruiz B, Pérez-López AM, et al. Cancer-derived exosomes loaded with ultrathin palladium nanosheets for targeted bioorthogonal catalysis. Nat Catal. 2019;2(10):864–872. doi:10.1038/s41929-019-0333-4.
   PubMed Web of Science ®Google Scholar
• Wei Z, Zhang X, Yong T, et al. Boosting anti-PD-1 therapy with metformin-loaded macrophage-derived microparticles. Nat Commun. 2021;12(1):1–20. doi:10.1038/s41467-020-20723-x.
   PubMed Web of Science ®Google Scholar
• Mortezaee K, Shabeeb D, Musa AE, et al. Metformin as a radiation modifier; implications to normal tissue protection and tumor sensitization. Curr Clin Pharmacol. 2019;14(1):41–53. doi:10.2174/1574884713666181025141559.
   PubMed Web of Science ®Google Scholar
• Rao L, Wu L, Liu Z, et al. Hybrid cellular membrane nanovesicles amplify macrophage immune responses against cancer recurrence and metastasis. Nat Commun. 2020;11(1):1–13. doi:10.1038/s41467-020-18626-y.
   PubMed Web of Science ®Google Scholar
• Van Beek AA, Van den Bossche J, Mastroberardino PG, et al. Metabolic alterations in aging macrophages: ingredients for inflammaging? Trends Immunol. 2019;40(2):113–127. doi:10.1016/j.it.2018.12.007.
   PubMed Web of Science ®Google Scholar
• Blacher E, Tsai C, Litichevskiy L, et al. Aging disrupts circadian gene regulation and function in macrophages. Nat Immunol. 2022;23(2):229–236. doi:10.1038/s41590-021-01083-0.
   PubMed Web of Science ®Google Scholar
• Mortezaee K, Khanlarkhani N, Sabbaghziarani F, et al. Preconditioning with melatonin improves therapeutic outcomes of bone marrow-derived mesenchymal stem cells in targeting liver fibrosis induced by CCl4. Cell Tissue Res. 2017;369(2):303–312. doi:10.1007/s00441-017-2604-1.
   PubMed Web of Science ®Google Scholar
• Mortezaee K, Pasbakhsh P, Kashani IR, et al. Melatonin pretreatment enhances the homing of bone marrow-derived mesenchymal stem cells following transplantation in a rat model of liver fibrosis. Iran Biomed J. 2016;20(4):207.
   PubMedGoogle Scholar
• Samec M, Liskova A, Koklesova L, et al. Metabolic anti-cancer effects of melatonin: clinically relevant prospects. Cancers. 2021;13(12):3018. doi:10.3390/cancers13123018.
   PubMed Web of Science ®Google Scholar
• Mortezaee K, Majidpoor J. NK and cells with NK-like activities in cancer immunotherapy-clinical perspectives. Med Oncol. 2022;39(9):131. doi:10.1007/s12032-022-01735-7.
   Web of Science ®Google Scholar