DOI: 10.6084/m9.figshare.24115064
title: Additional file 1 of Establishment of a high-fidelity patient-derived xenograft model for cervical cancer enables the evaluation of patient’s response to conventional and novel therapies

description: Additional file 1: Fig. S1 Histological characteristics of primary tumors and paired PDX models. a. The histological features of cervical cancer primary tumors and corresponding PDX tumors were assessed by hematoxylin and eosin staining in three patients. b. Quantitation of the epithelial and stromal components of the tumor and corresponding PDXs. Fig. S2 Genomic characteristics of primary tumor and paired PDX models. a. Whole-exome sequencing-based estimates of the purity and tumor ploidy of 10 paired samples. b. The percentage of the SNP genome discordance between PT and P1, or between P1and P2. c. AID/APOBEC mutational signatures (signatures 2 and 13) in PDXs. Fig. S3 Gating strategy of immune cell subsets in the tissues of primary tumors a. Gating strategy used for the analysis of leukocyte and T-cell subpopulations. b. The proportions of Treg and Trm in the engrafter and non-engrafter groups. c and d. The proportions of TEMRA, TEM, TCM, TN, and PD-1 positive fraction in CD4+ and CD8+ T cells in the engrafter (n = 6) and non-engrafter (n = 4) groups. These data are represented as the mean ± standard error. Statistical analyses were performed using the Mann–Whitney U test. Fig. S4 Tumor immune microenvironment of rapid engrafters and slow and non-engrafters. a. The proportions of T, B, and natural killer cells, monocytes, and T-cell subpopulations. (Rapid engrafters [n = 6] and slow and non-engrafters [n = 13]). b. The proportions of TEMRA, TEM, TCM, TN, and PD-1 positive fraction in CD4+ and CD8+ T cells in rapid-engrafters (n = 4) and slow- and non-engrafters (n = 6) groups. c. The proportions of immune cell subsets in the tumor according to the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts. Rapid engrafters (n = 10), slow and non-engrafters (n = 16). These data are represented as the mean ± standard error. Statistical analyses were performed using the Mann–Whitney U test. Fig. S5 Transcriptome profiles of rapid and slow and non-engrafters. a. Volcano plots illustrating the differentially expressed genes (DEGs) of primary tumors that were successfully engrafted (n = 16) versus those that were not successfully engrafted (n = 10). In total, 564 DEGs (258 upregulated and 306 downregulated) were founded. b. The gene set enrichment analysis of rapid engrafters. Fig. S6 Pathological characteristics of primary tumor tissue and PDX in two cervical cancer patients with chemotherapy. a. Pre-surgery imaging of cervical cancer lesions in patient CAT105. c. Imaging of cervical cancer lesions in patient CAT001 at the time of 3 years after treatment. b and d. Hematoxylin and eosin staining and α-smooth muscle actin, p16, and Ki67 staining for the primary tumor and paired PDX tumor of patient CAT001 and CAT105 (20× magnification). Fig. S7 In vitro and in vivo assessment of HER 2-targeted and adaptive tumor-infiltrating lymphocyte (TIL) combinative therapy strategies. a. HER2 mutation (P1170A: c.3508C&gt;G) was found in primary tumor, PDX and PDXO. b. T-cell populations in the immune cell infiltration of patient CAT001 were determined by flow cytometry. c. T-cell subpopulations in the TIL culture products of patient CAT001 were determined by flow cytometry. d. The body weight of the mice in different groups. e. Multiplex immunofluorescent images of CD4, CD8, and p16 positive cells in the tumor tissue of TIL and TIL combined neratinib treatment groups. Table S1. Primary antibodies used in this study. Table S2. Chemicals and recombinant proteins used in this study. Table S3. The clinicopathological characteristics of CC patients with rapid-engrafment (n = 25) and slow- engrafment (n = 19)