Genomic profiling and gene panel measurement of patients treated with sintilimab
choroid plexus papillary carcinoma, cancer, tumor, TNF-α
DISEASE, CANCER, TUMOR, PATHOGENESIS
In this study, we conducted WES of 15 patients to comprehensively characterize the mutational landscape of advanced and refractory pediatric patients. Our genomic analyses revealed that certain genetic alterations in important pathways occurred more frequently in the nonresponse group (SD/PD) patients compared to the response group (CR/PR) patients. G-protein-coupled receptors (GPCRs), constituting the largest gene family of cell membrane-associated molecules, actively engaged in signal transmission, have been linked to therapy resistance and immune evasion.Genomic profiling was conducted using WES on both FFPE tumor and matched peripheral blood samples obtained from 15 eligible subjectsPrevious investigations have reported that both the PI3K and MAPK pathways are involved in PD-1/PD-L1 regulation.Our study revealed differences in copy number losses and gains between the CR/PR group and the PD/SD group. Copy number losses of PDGFA and CDK15 and copy number gains of ABCD2 were observed in the nonresponse group, whereas the CR/PR group had copy number losses of E2F1 and GGT7 and copy number gains of PLEKHA3 and TRIM21. Further investigation is needed to clarify the functional outcomes associated with these CNVs related to the response to ICIs We further analyzed the microsatellite stability status of these patients. Supplementary Fig. In a separate case, a 5-year-old girl was diagnosed with choroid plexus papillary carcinoma. The disease progressed after multiple lines of chemotherapy. Subsequently, high-throughput sequencing of cancer gene mutations (295 genes related to cancer pathogenesis and targeted therapy) was performed. Mutations in TP53, ROS1, FANCD2, NOTCH1, and MEF2B were identified, with a tumor mutational burden (TMB) of 8.16 mut/Mb. The patient met the inclusion criteria and received treatment with sintilimab, resulting in disease control with a median PFS of 39 weeks.Peripheral blood samples were obtained from patients receiving sintilimab before and after 2 treatment cycles. Quantification of nine cytokines was performed. The results demonstrated that after 2 cycles of anti-PD-1 treatment, the levels of IFN-γ, TNF-α and IL-4 were significantly upregulated, while the level of IL-9 was downregulated. The levels of other cytokines and the ratios of IL-1b, IL-7, IP-10, MIP-1b, and RANTES remained similar in pre- and post-treatment plasma samples 