RESUMO
BACKGROUND: Treatment of non-small lung cancer (NSCLC) has evolved in recent years, benefiting from advances in immunotherapy and targeted therapy. However, limited biomarkers exist to assist clinicians and patients in selecting the most effective, personalized treatment strategies. Targeted next-generation sequencing-based genomic profiling has become routine in cancer treatment and generated crucial clinicogenomic data over the last decade. This has made the development of mutational biomarkers for drug response possible. METHODS: To investigate the association between a patient's responses to a specific somatic mutation treatment, we analyzed the NSCLC GENIE BPC cohort, which includes 2,004 tumor samples from 1,846 patients. RESULTS: We identified somatic mutation signatures associated with response to immunotherapy and chemotherapy, including carboplatin-, cisplatin-, pemetrexed- or docetaxel-based chemotherapy. The prediction power of the chemotherapy-associated signature was significantly affected by epidermal growth factor receptor (EGFR) mutation status. Therefore, we developed an EGFR wild-type-specific mutation signature for chemotherapy selection. CONCLUSION: Our treatment-specific gene signatures will assist clinicians and patients in selecting from multiple treatment options.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Receptores ErbB/genética , Idoso , Prognóstico , Estudos de Coortes , Biomarcadores Tumorais/genética , Imunoterapia , Carboplatina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pemetrexede/uso terapêutico , Medicina de Precisão , Sequenciamento de Nucleotídeos em Larga Escala , Antineoplásicos/uso terapêuticoRESUMO
Dendritic cells (DCs) play critical roles in recognizing and presenting antigens to T cells. They secrete dendritic cell-derived extracellular vesicles (DC-sEVs), which could mimic the function of DCs. Therefore, we explore the possibility of using DC-sEVs as a potential personalized vaccine in this study. We compared the efficacy of DCs and DC-sEVs on stimulating the immune system to target breast cancer cells and found that DC-sEVs had significantly more MHC molecules on the surface when compared to the parental DCs. In our in vivo and in vitro testing, Dc-sEVs showed significant advantages over DCs, regarding efficacy, safety, storage, and potential delivery advantages. DC-sEVs were able to suppress the growth of immune-cold breast tumors, while DCs failed to do so. These results indicate the strong potential utility of DC-sEVs as a personalized immunotherapy for breast cancer.