Fig. 5
From: Cancer cells avoid ferroptosis induced by immune cells via fatty acid binding proteins
Knockdown of FABP7 restores sensitivity to immunotherapy in resistant tumors. A, B Flow cytometry analysis of apoptosis with Annexin-specific antibody in CD8 + T cells co-cultured with Res-ctrl, Res-shFabp7, B16F10-ctrl, or B16F10-shFabp7 cells. Each group consisted of n = 3 technical replicates, with statistical analysis performed using Student's t-test. C, D Flow cytometry analysis of apoptosis in CD8+ T cells isolated from Cd8 cre;Rorafl or Rorafl mice, co-cultured with Res-ctrl or Res-shFabp7 cells. Each group consisted of n = 3 technical replicates, with statistical analysis performed using Student's t-test. Data represent findings from two independent experiments. E–H Flow cytometry analyses showing increased CD8 + T cell infiltration and reduced apoptosis in tumors with Fabp7 knockdown (Res-shFabp7 [in 129 Ev mice] or B16F10-shFabp7 [in C57BL/6 mice]) treated with either IgG or PD1. Each group consisted of n = 4 or 5 mice, with data analyzed using Student's t-test. Data represent findings from two independent experiments. I Assessment of the response of PD1-resistant tumors, with or without Fabp7 knockdown, to PD1 inhibition in 129 Ev mice (n = 5 per group), demonstrating enhanced sensitivity in Fabp7-knockdown tumors. Data analyzed using two-way analysis of variance. Data represent findings from at least 3 independent experiments. J Enhanced response of B16F10 melanoma tumors with Fabp7 knockdown to PD1 inhibitor treatment in C57BL/6 mice (n = 5 per group), demonstrating that Fabp7 knockdown improves tumor sensitivity to immunotherapy. Data analyzed using two-way analysis of variance. Data represent findings from two independent experiments. K Comparison of tumor growth in Cd8 cre;Rorafl mice injected with B16F10 cells and treated with either IgG control or PD1 (10 mg/kg) inhibitor (n = 5 per group) twice a week showed no significant difference in tumor growth. L Additional experiments with Res-ctrl and Res-shFabp7 cells in Cd8 cre;Rorafl mice (n = 5 per group) revealed a significant response to PD1 inhibition only in Fabp7-knockdown tumors, underscoring the importance of Fabp7 in resistance to PD1 inhibitor. Data analyzed using two-way analysis of variance. Data represent findings from two independent experiments