Fig. 7
From: KRASG12C inhibition using MRTX1257: a novel radio-sensitizing partner
RT and MRTX1257 reshape the tumor immune microenvironment in CT26 KRASG12C+/+ tumors. Flow cytometry analyses were performed in single-suspensions derived from CT26 KRASG12C+/+ tumors. Results are represented in mean ± standard-error to mean (SEM). Each point represents a single tumor in both the untreated control group (NIR + VEHICLE) and the group treated with RT alone (IR 6 Gy + VEHICLE). Each point represents 2 different tumors pooled in a single sample in both the group treated with MRTX1257 alone (NIR + MRTX1257) and the group treated with combined RT and MRTX1257 (IR 6 Gy + MRTX1257). n = 3/group. Except for dendritic cells, the proportions of the different immune cell subtypes are expressed in percentage in viable cells whereas the expression of PD-L1, major histocompatibility complex II (MHC II), and CD80 are expressed in the difference in mean fluorescence intensity compared to an unstained control within each condition (Delta MFI). NS: non-significant; *: p < 0.05; **: p < 0.01; ***: p < 0.001; ****: p < 0.0001 (one-way ANOVA) A BALB/c mice were subcutaneously inoculated with CT26 KRASG12C+/+ cells. Once the tumors reached an average volume of 90–100 mm3, mice received via oral administration 50 mg/kg of MRTX1257 or vehicle. The day after, mice received a single fraction of 6 Gy on the tumor mass. MRTX1257 at the dose of 50 mg/kg or vehicle were then administered at D1 and D3 after RT. At D4 after RT, mice were sacrificed, tumors were harvested and were used to perform flow cytometry. B Expression of PD-L1 in tumor and stromal CD45− cells. Mean ± SEM (left panel) and histogram overlay (right panel). C Proportion of lymphoid cells, conventional CD4 + T cells, CD8 + T cells and Tregs. D Proportion of myeloid cells and expression of PD-L1 within myeloid cells. E Proportion of dendritic cells type 2 (cDC2) in percentage of myeloid cells and expression of MHC II within cDC2. F Proportion of inflammatory monocytes and expression of MHC II within inflammatory monocytes. G Proportion of macrophages and expression of CD80 within macrophages