Figure 6 from ATM Regulates Differentiation of Myofibroblastic Cancer-Associated Fibroblasts and Can Be Targeted to Overcome Immunotherapy Resistance
Year: 2025
Type: other
Abstract: Targeting myofibroblast ATM promotes tumor CD8 T-cell infiltration and potentiates immunotherapy. A and B, Representative IHC staining (A) and relative quantification (B) of CD8 T cells in the core and periphery of TC-1 myo-rich tumors (described in Fig. 5F–J; ntr = FoV = 10; dotted lines, tumor margins). C and D, Representative IHC staining (C) and relative quantification (D) of CD8 T cells in the core and periphery of tumors described in Fig. 5K (ntr = FoV = 10). E and F, Flow cytometry analysis from TC-1 + myo-rich tumors described in Fig. 5K (E shows two experiments; two-way ANOVA was used). G and H, Representative IHC staining (G) and relative quantification (H) of CD8 T cells in the core and periphery of the tumors described in Fig. 5P (ntr = FoV = 10). I–L, Mice were injected with TC-1 + myoMLF and treated with RAH vaccine±AZD0156. Control plasmid with vehicle was used as control. Tumor growth curves of a representative experiment (I; mouse number = 7–8; see also Supplementary Fig. S7A); two-way ANOVA is shown and refers to AUC analysis of three experiments (J). Representative IHC staining (K) and relative quantification (L) of CD8 T cells in the tumor core (ntr = FoV = 10). M–P, Mice were injected with MC38 and myoMCF and treated with αPD-1 and AZD0156, either alone or in combination. Control mice received isotype control antibody and vehicle. Tumor growth curves of a single experiment (M; mouse number = 5–8; see also Supplementary Fig. S7B) and relative AUC analysis (N). Representative IHC staining (O) and relative quantification (P) of CD8 T cells in the tumor core (ntr = FoV = 10 in P). Q and R, Overall survival of mice injected with TC-1 + myoMLF (Q) or MC38 + myoMCF (R) and treated as indicated (mouse number = 7–8 for both experiments; Mantel–Cox log-rank test is shown; see also Supplementary Fig. S7C and S7D). Scale bars, 200 μm. A homoscedastic Student t test is used throughout the figure and is relative to the control unless otherwise highlighted. ns, nonsignificant; *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001; ****, P ≤ 0.0001.
Authors: Massimiliano Mellone, Klaudia Piotrowska, Giulia Venturi, Lija James, Aleksandra Bzura, Maria A. Lopez, Sonya James, Chuan Wang, Matthew J. Ellis, Christopher J. Hanley, Josephine F. Buckingham, Kerry L. Cox, Gareth Hughes, Viia Valge-Archer, Emma V. King, Stephen A. Beers, Vincent Jaquet, George D.D. Jones, Natalia Savelyeva, Emre Sayan, Jason L. Parsons, Stephen Durant, Gareth J. Thomas
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4416587800