Fig. 7: Efficiency of combinatory treatments for breast cancer. | Nature Communications

Fig. 7: Efficiency of combinatory treatments for breast cancer.

From: S100A9-CXCL12 activation in BRCA1-mutant breast cancer promotes an immunosuppressive microenvironment associated with resistance to immunotherapy

Fig. 7

a, b Representative tumor images (a) and volume (b) from Balb/C mice after 35 days pad implantation with EMT6-Ctr cells, sgS100A9-EMT6, and sgCxcl12-EMT6 cells at 1 × 106 cells per fat pad (n = 15 mice). c Proliferation of EMT6 cells and EMT6 cells expressing either sgS100a9 or sgCxcl12 in vitro. d The percent of different immune cells in tumor tissues without or with expression of sgS100a9 and sgCxcl12 in Balb/C mice by CyTOF analysis with antibodies to CD3/CD4, CD3/CD8, CD11b/Ly6G, CD11b/Ly6C, and CD3/CD28 (n = 3 mice/group). e CXCL12 expression in either BRCA1-high and S100A9-low (n = 498) or BRCA1-low and S100A9-high (n = 160) breast cancer patients from the TCGA breast database. f Overall survival of breast cancer patients with low expression of BRCA1 and high expression of S100A9 from the GSE19783-GPL6480 database (n = 216). g, h Tumor volumes and representative images of tumors formed from 231 cells without or with expression of sgS100A9 in nude mice (n = 9 mice/group). il Outline of treatment strategy with PBS (n = 10 mice), PD1 antibody (n = 6 mice), Tas (n = 3 mice), or PD1 antibody together with Tas (n = 5 mice) for Brca1-MT mice (i). Volumes and numbers of tumors (j), representative images of lungs and livers (k), and sections of the primary tumor (l) before treatment (left) and the residual mammary tissue of the same mouse after treatment (right). PD1 antibody was administered at day one (D1) and D21, respectively, after removing the primary tumor when the size of tumors reached 1 cm in size. Other drugs were used every day starting from D2. m, n Tumor images (m) and volume (n) at D29 from FVB mice with fat pad implantation of 545 cells and treatment with PBS and αPD1 (n = 7 mice/group). o, p Tumor volumes and representative images at the D29 from FVB mice with implantation of 545 cells (4 × 106 cells/fat pad) and treatment with PBS (n = 6 mice), AMD3465 (AMD) + αPD1 (n = 7 mice), and Tas + αPD1 (n = 7 mice). q, r Immune cell populations in CD45+ cells from the same cohorts of mice in (M-P) by CyTOF analysis at D13 and D29 (n = 3 mice/group, CyTOF gating strategies see in Supplementary Fig. 8a). The data are expressed as means ± SD (b, d, g, j, n, p) and P values determined by unpaired two-tailed Student’s t test (g, n) and by one-way ANOVA followed by Tukey’s multiple comparisons (b, d, j, p, q, r). The experiments were independently repeated three times with similar results (c). Scale bar: black color, 100 μM. Source data are provided as a Source data file.

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