Extended Data Fig. 9: Apoptotic cancer cells are effectively phagocytosed by reprogramed TAMs.

a, b, Schematic diagrams showing bone marrow (BM) chimera mice to define TAM engulfment of dying cancer cells. BM cells from homozygous H2B-EGFP/H2B-EGFP mice were transferred into lethally irradiated S100a8-cre-Rosa26^{LSL-MYC/LSL-H2B-mCherry}PyMT recipients with a tumor burden around 250-350 mm³ followed by switching to a low protein (LP) diet (2% protein in weight, 5BT9, TestDiet) two weeks after. c, A schematic diagram showing dietary treatment of BM chimera mice. BM cells of control or Fcgr1-cre-Pikfyve^fl/fl mice were transferred into lethally irradiated S100a8-cre-Rosa26^{LSL-MYC/LSL-H2B-mcherry}PyMT recipients with a tumor burden around 250–350 mm³, which were either kept under a normal protein (NP) diet (15% protein in weight, 5CC7, TestDiet) condition or switched to a LP diet two weeks after. d, RT-qPCR analysis of PIKfyve mRNA expression in TAMs of the indicated genotypes (n = 4 mice for each group). e, A schematic diagram showing dietary treatment of BM chimera mice. BM cells from control or Fcgr1-cre-Pikfyve^fl/fl mice were transferred into lethally irradiated S100a8-cre-Rosa26^LSL-MYC/+PyMT or S100a8-cre-Rosa26^LSL-MYC/+Pikfyve^fl/flPyMT recipients with a tumor burden around 250-350 mm³ followed by switching to a LP diet two weeks after. f, Experimental design of an in vivo engulfment assay with intratumoral injection of CellTrace Violet (CTV) and CellTrace Yellow (CTY)-labeled apoptotic cells and apoptotic bodies. g,h, Experimental design and flow cytometry analysis of an ex vivo engulfment assay with TAMs and cancer cells fed with apoptotic cells and apoptotic bodies in a low amino acid RPMI medium (1: 4 mixtures of RPMI and amino acid-free RPMI). n = 3 independent experiments and cells from independent mice each group. All statistical data are shown as mean ± S.D. Two-sided Student t-test in (d), one-way ANOVA with the Tukey multiple comparison test correction in (h).

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