Journal: Cancer Communications
Article Title: Metabolic landscape of head and neck squamous cell carcinoma informs a novel kynurenine/Siglec‐15 axis in immune escape
doi: 10.1002/cac2.12545
Figure Lengend Snippet: Siglec‐15 specific siRNA delivered by NH 2 ‐MSN nanoparticles enhances immunotherapy efficacy in vivo. (A) Synthesis routes of NH 2 ‐MSN nanoparticles loaded with siRNA. (B) Macroscopy characterization of NH 2 ‐MSNs with siS15. (C) Transmission electron microscopy images of NH 2 ‐MSNs and NP‐siS15 with indicated ratios. (D‐E) The morphology and Zeta potential of NH 2 ‐MSNs and NP‐siS15. (F) Scanning microscopy analysis of the cellular uptake of NH 2 ‐MSNs with or without the indicated siS15‐Cy5 by SCCVII cells after in vitro treatment for 24 h. (G) Western blotting analysis confirming Siglec‐15 gene‐silencing effect by siRNA released from nanoparticles in SCCVII cells. (H) Schematic diagram of the treatment strategy in SCCVII mouse model. (I) Probability of survival analysis for each group was performed. (J) Analysis of TUNEL and Ki‐67 staining of tumor tissues in each group. (K‐L) The percentage of CD3 + CD8 + (K) and PD‐1 + cells in CTLs (L) of the indicated treatment groups. (M) Analysis of multiplex immunofluorescence staining of CD3 + (green) and CD8 + (red) were shown and quantification analysis were performed in tumor tissues ( n = 10 fields of five mice per group). (N) Schematic diagram of the anti‐PD‐L1 and NP‐siS15 combination treatment strategy in C3H/He subcutaneous tumorigenesis models. (O‐P) Tumor volume and weights were measured and analyzed in the indicated groups. Data are represented as mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, ns: not significant. Abbreviations: siS15, Siglec‐15 small interfering RNA; DAPI, 4',6‐diamidino‐2‐phenylindole; AhR, aryl hydrocarbon receptor; NP‐siS15, NH 2 ‐MSN‐si SIGLEC15 ; DAPI, 4',6‐diamidino‐2‐phenylindole; siScr, siScramble; anti‐PD‐1, anti‐programmed cell death protein 1 antibody; TUNEL, TdT‐mediated dUTP‐biotin nick end labeling; CTL, cytotoxic T lymphocyte; anti‐PD‐L1, anti‐programmed death‐ligand 1 antibody; SEM, tandard error of the mean; ns, not significant.
Article Snippet: SCCVII cells were transfected with NH 2 ‐MSNs that contained siS15 (RiboBio) labeled with Cyanine (Cy) 5 (NP‐siS15‐Cy5).
Techniques: In Vivo, Transmission Assay, Electron Microscopy, Zeta Potential Analyzer, Microscopy, In Vitro, Western Blot, TUNEL Assay, Staining, Multiplex Assay, Immunofluorescence, Small Interfering RNA, End Labeling
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