Fig. 5: FAP-IL2v enhances ADCC through NK activation. | Nature Communications

Fig. 5: FAP-IL2v enhances ADCC through NK activation.

From: Targeted immunotherapy against distinct cancer-associated fibroblasts overcomes treatment resistance in refractory HER2+ breast tumors

Fig. 5

a, b Relative gene expression levels of (a) CD45 and NCR1, (b) PRF1, GZMB and IFNG measured by qRT-PCR in HER2+ 3DiBCs (HCC1954/BF2) treated as indicated. IgG1 was used as control for TTZ. n = 3 biologically independent experiments. Values are mean ± s.d. c Flow cytometry analysis using gating panels from Supplementary Fig. 4e and showing percentages of NK cells, CD16+ NK cells and NKT cells in infiltrating ICs from HER2+ 3DiBCs (HCC1954/BF2) treated with trastuzumab (T) or trastuzumab + FAP-IL2v (T/F) compared to control (IgG1; C). n = 6 biologically independent experiments. d Flow cytometry profiles illustrating data from (c). e GSEA of CD56+ NK and CD56+CD3+ NKT cells gene signatures comparing pCR vs. RD (left panels) and Rel vs. RF (right panels) HER2+ BC after TTZ-based therapy. f Growth kinetics of macroscopic tumors derived from subcutaneous injection of HCC1954 cells into nude mice treated with DP47-IL2v (dashed blue; n = 11), FAP-IL2v (dashed red; n = 12), TTZ (gray; n = 8), TTZ/DP47-IL2v (blue; n = 12), TTZ/FAP-IL2v (red; n = 11) compared to control (IgG1; dashed gray; n = 7). Values are mean ± s.e.m. g Bioluminescent tracking of HCC1954 in HER2+ 3DiBCs treated with TTZ, FAP-IL2v, DP47-IL2v, and/or blocking antibody against CD16 in presence of NK cells. n = 4 (HCC1954/BF1; blue) and n = 9 (HCC1954/BF2; red) HER2+ 3DiBCs examined per condition, from 3 biologically independent experiments. Values are mean ± s.e.m. pCR pathological complete response, RD residual disease, Rel relapsing patients, RF relapse-free patients, ES enrichment score, NES normalized enrichment score, FDR false discovery rate, TTZ trastuzumab, RLU relative luminescence units. Two-sided, unpaired (a, b, f, g) and paired (c) t test p values (P) are indicated. GSEA nominal p value (P) and FDR-adjusted p value are indicated for (e). Source data are provided as a Source Data file.

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