Fig. 7

TIM could predict breast cancer immunotherapy response, especially for anti-PD-L1 therapy. a Rates of response to immunotherapy in TIM high and low expression groups by TIDE scores. The TIDE algorithm was used to predict the immunotherapeutic responses of BRCA patients in the TCGA dataset. Significance was tested using a χ² test. b Correlation analyses between TIM and TIDE scores, including dysfunction of tumor infiltrating CTL, CAF and MDSC. Significance was tested using Spearman's rank correlation. c The lollipop chart showed the correlation between TIM and immune checkpoint genes in TCGA dataset. d 4T1 transplanted breast cancer mice model in GSE130472 received anti-PD-L1 therapy and anti-CTLA4 therapy (TISMO). TIM mRNA expression level didn’t change despite different immune treatments (TISMO). Better therapeutic therapy response to anti-PD-L1 therapy was seen in mice with higher TIM mRNA expression level in GSE130472 (TISMO). Significance was tested using the Student’s t-test. e Survival analysis of high and low PD-L1 in the total population and subgroups based on different TIM expression levels with the TCGA dataset. Significance was tested using the Cox regression analysis. f Representative PD-L1 immunohistochemical (IHC) images based on different TIM expression levels using tumor tissue of the RENJI cohort. The scatter plot on the right showed that PD-L1 IHC expression levels were relatively higher in patients with relatively higher TIM expression. The scale bar is 50 μm. Significance was tested using the Student’s t-test. g Expression of PD-L1 mRNA expression level in the RENJI cohort of patients with relatively higher TIM and lower TIM expression. The mRNA expression level was analyzed by RT-qPCR. β-actin was used as the internal reference. Significance was tested using the Student’s t-test. Significance was tested as described above: ns, p-value no significance; *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001. TIDE tumor immune dysfunction and exclusion, CTL cytotoxic T lymphocyte, CAF tumor-associated fibroblast, MDSC myeloid-derived cell