Fig. 7: Targeting ID1 inhibits CRC progression and sensitizes tumor cells to chemotherapy and immunotherapy.

a Schematic diagram for evaluating the therapeutic effects of ML323. b, c Tumor volumes (b), representative images (left) and quantification (right) of CD8+ T cell infiltration (c) of the indicated groups presented in (a), n = 8 (b), or 5 (c) mice per group, Welch’s test. Scale bar, 20 μm. d CD44 expression in the indicated groups. e The therapeutic effects of ML323 in the liver metastasis model. f–i Representative gross images of metastatic sites (f), number of hepatic lobes with metastatic tumor (g), the percentage of CD8+ T cells (h), and flow cytometry of CD44 in CD45- Epcam+ cells (i) of the indicated groups presented in (e). n = 5 mice per group in f–h, Welch’s test. n = 3 biologically independent samples in (i), Student’s t-test. Scale bar, 1 cm. j, k Therapeutic effects of ML323 in Id1f/f or Id1Lyz-KO tumor-bearing mice. Tumor weight (j) and tumor inhibition rate (k) were shown, n = 6 mice per group, one-way ANOVA test (j), Student’s t-test (k). l Schematic diagram for isolating TAMs from indicated mice. m The migration rate of CD8+ T cells cocultured with TAMs isolated as presented in (l), n = 5 mice per group. n CD44high Aldh+ cell ratio of CT26 cells cocultured with TAMs isolated as presented in (l), n = 3 mice per group. o Migration of CD8+ T cells when cocultured with Id1f/f or Id1Lyz-KO TAMs under ML323 (10 μM) treatment, n = 3 biologically independent samples, one-way ANOVA test. p CD44 expression in CT26 cells cocultured with Id1f/f or Id1Lyz-KO TAMs under ML323 (10 μM) treatment, n = 3 biologically independent samples. q, r Effects of ML323 on expression of Serpinb2 (q) and Ccl4 (r) in the indicated groups, n = 4 biologically independent samples. s Therapeutic effects of ML323 with 5-FU. Comb: ML323 + 5-FU. t–v Tumor volumes (t), tumor weight (u), and representative tumor images (v) of indicated groups in (s), n = 6 mice per group, one-way ANOVA test. Scale bar, 1 cm. w Therapeutic effects of ML323 with CTLA4-Ab. Comb: ML323 + CTLA4-Ab. x Tumor volumes of indicated groups in (w), n = 6 mice per group, one-way ANOVA test. y Tumor weight of indicated groups in (w), n = 8, 7, 8 and 7 in the groups of Vehicle, ML323, CTLA4-Ab, and Comb, one-way ANOVA test. z Representative tumor images of indicated groups in (w). Scale bar, 1 cm. Elements of a, e, j, l, s, and w are created with BioRender.com. Source data are provided as a Source Data file.