Fig. 2

Cirrhotic-ECM and Col1 attenuated aPD-1 therapy by interrupting T cell cytotoxicity in clinical cohorts and pre-clinical models. A Correlation between GSEA enrichment score of ECM composition and C-ECM score in TCGA LIHC cohort. B, C TIDE score and ECM composition enrichment in 2 melanoma cohort treated with aPD-1 in TCGA cohort. D Heatmap of pan-cancerous correlation between TIDE score and collagen genes. E, F Sirius red staining of collagen fiber in aPD-1-treated HCC patients with well (n = 19) or poor responses (n = 12). Scale Bar: 500 μm. G Representative MRI images of the different response HCC patients to aPD-1 treatment. H Establishment scheme of Hepa1-6 orthotopic implantation HCC model in C57BL/6 mice w/o cirrhotic-ECM alteration. I, J Representative bioluminescence images of tumors w/o aPD-1 treatment in orthotopic implantation HCC model w/o ECM alteration (I), and quantification of average radiance of fluoresce intensity of photon flux (J). K Quantification of Intratumor IFNγ+ T cell, PD-1+TIM3+ T cell and TIM3+ T cell across subgroups of orthotopic implantation HCC model w/o cirrhotic-ECM alteration by flow cytometry. L Establishment scheme of Hepa1-6 subcutaneous implantation HCC model in C57BL/6 mice w/o cirrhotic-ECM/Col1 alteration. M, N Images and quantification of tumor w/o aPD-1 treatment in subcutaneous implantation HCC model w/o cirrhotic-ECM/Col1 alteration. Scale Bar: 1 cm. O C value of ECM or Col1 under aPD-1 or control treatment challenge. X axis showed whether tumor underwent aPD-1 treatment challenge. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001