Extended Data Fig. 3: Tumor-induced changes in BM progenitors impact mo-mac fate and function in TME.
From: Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumours
a, Representative gating strategy for mouse lung myeloid populations. AM, alveolar macrophages. DC, dendritic cells. mo-mac, monocyte-derived macrophages. b, Representative plots for intratumoral TREM2hi mo-macs and CD86+MHCII+ mo-macs, overlaid on phenotypic markers Arg1, CD206, PDL1, CD73, CD11c. c, CD64+MERTK+ mo-macs differentiated from donor CD45.2+ GMPs of naïve or tumor-primed origin (related to Fig. 2a). d, Frequency of BMDMs expressing Arg1, PDL1, MHCII, CD86 upon in vitro differentiation with KP tumor conditioning early (48 hr) or no conditioning (no prime). n = 4 per group. e, Frequency of BMDMs expressing Arg1, MHCII, CD86, and Arg1hi mo-macs expressing PDL1 upon in vitro differentiation with KP tumor conditioning early (48 hr prime) followed by washout. n = 3 per group. f, Frequency of CellROX-, LiperFluo- (n = 5 per group), and MitoSOX-expressing Ly6Chi monocytes (n = 3 per group) in KP tumor-bearing lung at day 21. g, Median Fluorescence intensity (MFI) for CellROX in KP tumor-infiltrating mo-macs. n = 4 per group. h, Representative cytometry plots and frequency of NRF2+ and HO-1+ cells in KP tumor-infiltrating mo-mac subsets. n = 4 per group. i, NRF2 downstream gene activation per-patient score in lung-infiltrating myeloid cells from independent cohorts of NSCLC (Leader et al., n = 35 and Hu et al. n = 15 patients). j, Frequency of BMDMs expressing NRF2 and HO-1 after 48 h prime and washout of KP CM, related to Extended Data Fig. 3e, n = 3 per group. k, Frequency of intratumoral donor mo-macs expressing NRF2 and HO-1 four days after GMP transfer from naïve (n = 3) or tumor-primed (n = 5) origin into congenic tumor-bearing hosts (related to Fig. 2a). One experiment. l, Browser plots for H3K4me3 signal at known NRF2-associated gene loci in KP tumor-associated and naïve GMPs. Highlighted regions indicate differential signal near known cis-regulatory elements and open chromatin (OCR) containing Nfe2l2 motif. Individual data points with bar denoting mean, representative of two independent experiments. Statistics computed by one-way ANOVA with Tukey’s multiple comparison (d), one-way ANOVA with Dunnett’s multiple comparison (i), and unpaired two-tailed Student’s t-test (e)–(h),(j)–(k).
