Extended Data Fig. 3: XBP1 supports protumorigenic polarization in response to cancer-derived stimuli.

a, Immunoblots of indicated proteins in control or XBP1-deficient BMDMs stimulated with or without 1μM thapsigargin for 6 h. Data are representative results of two independent experiments. b, Quantification of BODIPY staining in BMDMs generated from WT (XBP1^wt) or KO (XBP1^cKO) mice cultured stimulated with regular culture medium (Ctrl) or YUMM1.7 CM (n = 12 per group). Data are pooled from three independent experiments. c, Percentages of TAMs (F4/80⁺ CD11b⁺ Gr1^-) among CD45⁺ cells in melanomas from tumor-bearing XBP1^wt (n = 5) and XBP1^cKO mice (n = 6). Data are representative results of three independent experiments. d, e, Tumor growth (d) and tumor weight (e) of YUMM1.7-OVA melanoma from WT and XBP1^cKO mice treated with PBS or with anti-CSF1R as indicated in the methods; XBP1^wt PBS (n = 13), XBP1^cKO PBS mice (n = 12), XBP1^wt αCSF1R (n = 12), XBP1^cKO αCSF1R (n = 13). Data are pooled from three independent experiments. f, percentages of TAMs (F4/80+ cells gated on CD11b + Gr1-) among CD45 + cells in the experiment showed in d, e (n = 8 per group for XBP1^wt PBS, XBP1^cKO PBS, XBP1^wt αCSF1R; n = 9 for XBP1^cKO αCSF1R). Data are pooled from two independent experiments. g, Representative plots of iTAMs and mTAMs populations in tumor and spleen of YUMM1.7 tumor-bearing. h–k, Representative histograms (up) and quantitative plots (down) of PDL1 (h), MHCII (i), sXBP1 (j) and ARG1 (k) expression in iTAMs and mTAMs from YUMM1.7 tumor-bearing mice (n = 6). Data are pooled from two independent experiments. l, Representative plots of iTAMs and mTAMs populations in tumor and spleen of Braf/Pten melanoma-bearing mice. m–p, Representative histograms (up) and quantitative plots (down) of PDL1 (m), MHCII (n), sXBP1 (o) and ARG1 (p) expression in iTAMs and mTAMs from Braf/Pten melanoma-bearing mice (n = 5). Data are representative of two independent experiments. Each symbol represents one individual. q–t, Tumor growth (q) and tumor weight (r) of B16-OVA melanoma and tumor growth (s) and tumor weight (t) of MC38-OVA colon adenocarcinoma in XBP1^wt (n = 9 for B16-OVA and n = 8 for MC38-OVA) or XBP1^cKO (n = 10 for B16-OVA and n = 7 for MC38-OVA) mice. Data are pooled from two independent experiments. Data are mean ± s.e.m. were analyzed by two-tailed, unpaired Student’s t-test.

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