Fig. 5: Uchl5-mediated control of Col17a1 expression contributes to immune evasion and ICB resistance in HNSCC.
From: In vivo CRISPR screening in head and neck cancer reveals Uchl5 as an immunotherapy target
A Expression of COL17A1 protein level across different cancer cell lines from the Cancer Cell Line Encyclopedia (CCLE) dataset, n = 4 − 69 samples per group. B Western blot and quantification of COL17A1 protein levels in control and Uchl5-deficient MOC1-esc1 cells, data is representative of two independent experiments. The samples derive from the same experiment, but COL17A1 and α-Tubulin were run on one gel, UCHL5 on another gel, both gels were processed in parallel under the same conditions. C, D Western blot and quantification of COL17A1 protein levels in control and Uchl5-deficient tumors harvest on day 16 after tumor inoculation, n = 7 tumors. The samples derive from the same experiment, COL17A1 and α-Tubulin were run on one gel. Data are representative of two independent experiments. E, FImmunohistochemistry (IHC) staining and quantification of COL17A1 in control or Uchl5-deficient tumors harvested on day 16 after tumor inoculation. n = 4 tumors for control group, 7 tumors for Uchl5-deficient tumors. G Tumor growth curves in mice challenged with control and Col17a1-deficient MOC1-esc1 tumor cells in NSG, WT C57BL/6 mice with or without anti-PD1 treatment. For the NSG group: n = 5 (Col17a1 sg1), n = 10 (Ctrl and Col17a1 sg2) tumors. For the WT group: n = 4 (Col17a1 sg1 untreated), n = 9 (Col17a1 sg1 PD1-treated); n = 10 (Ctrl untreated and Col17a1 sg2 untreated); n = 20 (Ctrl PD1-treated and Col17a1 sg2 PD1-treated) tumors. Data are representative of two independent experiments, and the comparisons are between Col17a1-deficient and control MOC1-esc1 tumor cells. H Western blot analysis of the expression of exogenously transduced COL17A1 in Uchl5-deficient MOC1-esc1 cells. The samples derive from the same experiment, COL17A1 and α-Tubulin were run on one gel, data is representative of two independent experiments. I Tumor growth and survival curves in WT C57BL/6 mice challenged with Uchl5-deficient MOC1-esc1 tumor cells with overexpression of either truncated human CD19 or mouse full-length COL17A1 with anti-PD1 treatment, n = 9 tumors for hCD19 group and 10 tumors for COL17A1 OE group, data are representative of two independent experiments. The samples derive from the same experiment, COL17A1 and α-Tubulin were run on one gel. Data in A was represented as mean ± s.d., Data in D and F were calculated by unpaired, two-sided Student’s t-test and are represented as mean ± s.d., data in (G) and (I) were analyzed by two-way ANOVA represented as mean ± s.e.m. Source data are provided as a Source Data file.
