Fig. 7

Cocultures between patients-derived spheroids and autologous TILs confirm therapeutic potential of MICA/B and NKG2A targeting. a and b Flow cytometry analyses of a NKG2A and b NKG2D expression by CD4 T cells, CD8 T cells and NK cells in the blood and tumor of colorectal cancer patients. n = 41 independent experiments. c Scheme of the protocol used to create primary colon tumor-derived spheroids and maintain autologous TILs in culture before cocultures. d Representation of the change in spheroid volume 48 h after coculturing or not primary CRC-derived spheroids and autologous TILs in the presence or not of IL-15, measured using microscopic pictures. e to g Change in spheroid volume 48 h after culturing primary CRC-derived spheroids with (f and g) or without (e) autologous TILs, in the presence or not of anti-MICA/B, anti-NKG2A or corresponding control isotypes. In d to f panels, spheroid volumes are normalized to the culture condition without stimulation. g panel represents fold changes between anti-MICA/B and its isotype, and between combination and combination of isotypes. In d to g panels, each patient is represented by a specific symbol. n = 5 independent experiments. Statistical significance of a and b panels was analyzed Wilcoxon matched-pairs signed rank test, the other panels using paired t test (* p < 0.05; ** p < 0.005, *** p < 0.001, **** p < 0.0001)