biostudies-literatureWang BPediatric Cancer Research FoundationMarcus FoundationNCI NIH HHSCalifornia Institute for Regenerative MedicineV Foundation for Cancer ResearchNIH HHS4238https://www.ebi.ac.uk/biostudies/studies/S-EPMC11674635biostudies-literatureUnknown16(24)<b>Background</b>: Macrophage-mediated cancer cell phagocytosis has demonstrated considerable therapeutic potential. While the initiation of phagocytosis, facilitated by interactions between cancer cell surface signals and macrophage receptors, has been characterized, the mechanisms underlying its sustentation and attenuation post-initiation remain poorly understood. <b>Methods</b>: Through comprehensive phosphoproteomic profiling, we interrogated the temporal evolution of the phosphorylation profiles within macrophages during cancer cell phagocytosis. <b>Results</b>: Our findings reveal that activation of the mTOR pathway occurs following the initiation of phagocytosis and is crucial in sustaining phagocytosis of cancer cells. mTOR inhibition impaired the phagocytic capacity, but not affinity, of the macrophages toward the cancer cells by delaying phagosome maturation and impeding the transition between non-phagocytic and phagocytic states of macrophages. <b>Conclusions</b>: Our findings delineate the intricate landscape of macrophage phagocytosis and highlight the pivotal role of the mTOR pathway in mediating this process, offering valuable mechanistic insights for therapeutic interventions.CancersPhosphoproteomic Profiling Reveals mTOR Signaling in Sustaining Macrophage Phagocytosis of Cancer Cells.PMC11674635Pediatric Cancer Research FoundationR01CA255250CLIN2-12153Marcus FoundationR01 CA255250R21CA280317R21 CA280317Pediatric translational awardR01CA258778INFR4-13587R01 CA258778Feng MCao XWang LDWang BManousopoulou APirrotte PWang YGarcia-Mansfield KZhou JfalsePhosphoproteomic Profiling Reveals mTOR Signaling in Sustaining Macrophage Phagocytosis of Cancer Cells.<b>Background</b>: Macrophage-mediated cancer cell phagocytosis has demonstrated considerable therapeutic potential. While the initiation of phagocytosis, facilitated by interactions between cancer cell surface signals and macrophage receptors, has been characterized, the mechanisms underlying its sustentation and attenuation post-initiation remain poorly understood. <b>Methods</b>: Through comprehensive phosphoproteomic profiling, we interrogated the temporal evolution of the phosphorylation profiles within macrophages during cancer cell phagocytosis. <b>Results</b>: Our findings reveal that activation of the mTOR pathway occurs following the initiation of phagocytosis and is crucial in sustaining phagocytosis of cancer cells. mTOR inhibition impaired the phagocytic capacity, but not affinity, of the macrophages toward the cancer cells by delaying phagosome maturation and impeding the transition between non-phagocytic and phagocytic states of macrophages. <b>Conclusions</b>: Our findings delineate the intricate landscape of macrophage phagocytosis and highlight the pivotal role of the mTOR pathway in mediating this process, offering valuable mechanistic insights for therapeutic interventions.2024-01-01T00:00:00Z2024 Dec2026-04-08T19:00:31.838Z2026-04-08T11:28:39.858ZS-EPMC116746353976613710.3390/cancers16244238