Fig. 7
HCC patients whose spatial isolated ATP–adenosine pathway was activated by tumor–macrophage communication show poor response to PD1 antibody therapy. a Bar plot indicating the change in tumor size in the nine patients after treatment with PD1 antibody nivolumab. Evaluation by iRECIST, the blue bar represents PR (partial response, n = 4) and the red line represents PD (progressive disease, n = 5). b Representative PET-CT results show tumor size of two patients before and after PD1 antibody therapy (left patient: PD; right patient: PR). c tSNE plot of different major immune cell clusters in PBMCs from the nine patients (CD4 T: CD11b− CD4+ CD8− cells; CD8 T: CD11b− CD4− CD8+ cells; NK: CD11b− CD56+ cells; B cell: CD11b− CD19+ cells; cDC: CD11b− CD141+ cells; M1 like: CD11b+ CD163− cells; M2 like: CD11b+ CD163+ cells; unas.: unassigned cells). d Violin plot of different immune cell clusters in PBMCs from the nine PD, PR HCC patients after anti-PD1 therapy (CD4 T%: rate of CD4+ CD8− cells in gated CD11b− cells; CD8 T%: rate of CD4− CD8+ cells in CD11b− gated cells; NK%: rate of CD56+ cells in gated CD11b− cells; B %: rate of CD19+ cells in gated CD11b− cells; cDC %: rate of CD141+ cells in gated CD11b− cells; M1 like%: rate of CD163− cells in gated CD11b+ cells; M2 like%: rate of CD163+ cells in gated CD11b+ cells; Mann–Whitney test: *: p < 0.05, ns: not significant). e Fluorescence intensities of CD163 (PE-cy7) in CD11b+ cells from the nine patients are displayed as heatmap statistics by flow cytometry analysis. f Heatmap shows the correlation trends between level of exosomal circTMEM181 in blood serum and different immune cell clusters (Spearman correlation coefficient is indicated by heatmap). g tSNE plot of CD39+ cell clusters (red) in PBMCs from the nine patients. h Fluorescence intensities of CD39 (PE) in CD11b+ cells from the nine patients are displayed as heatmap statistics of flow cytometry analysis (Left). The statistical results show the mean fluorescence intensity (MFI) difference between the PD and PR groups among the nine patients (Right; Mann–Whitney test: p = 0.032). i Correlation between level of exosomal circTMEM181 in blood serum and MFI of CD39 (PE) in CD11b+ cells from PR or PD patients (simple linear regression: R2 = 0.45, p = 0.048). j Representative multi-label-immunofluorescence image showing CD39 expression on macrophages (CD68+), and CD73 expression on tumor cells (CK8+) in the tumor microenvironment of PD or PR HCC patients after PD1 antibody therapy