High hydrostatic pressure (HHP) induces immunogenic death of tumor cells which confer protective anti-tumor immunity in vivo. Moreover, DC pulsed with HHP-treated tumor cells induced therapeutic effect in mouse cancer model. In this study, we tested the immunogenicity, stability and T cell stimulatory activity of human monocyte-derived dendritic cell (DC)-based HHP lung cancer vaccine generated in GMP compliant serum free medium using HHP 250 MPa. DC pulsed with HHP-killed lung cancer cells and poly(I:C) enhanced DC maturation, chemotactic migration and production of pro-inflammatory cytokines after 24h. Moreover, DC-based HHP lung cancer vaccine showed functional plasticity after transfer into serum-containing media and stimulation with LPS or CD40L after additional 24h. LPS and CD40L stimulation further differentially enhanced the expression of costimulatory molecules and production of IL-12p70. DC-based HHP lung cancer vaccine decreased the number of CD4+CD25+Foxp3+ T regulatory cells and stimulated IFN-γ-producing tumor antigen-specific CD4+ and CD8+ T cells from non-small cell lung cancer (NSCLC) patients. Tumor antigen specific CD8+ and CD4+ T cell responses were detected in NSCLC patient’s against a selected tumor antigens expressed by lung cancer cell lines used for the vaccine generation. We also showed for the first time that protein antigen from HHP-killed lung cancer cells is processed and presented by DC to CD8+ T cells. Our results represent important preclinical data for ongoing NSCLC Phase I/II clinical trial using DC-based active cellular immunotherapy (DCVAC/LuCa) in combination with chemotherapy and immune enhancers.
These results confirm the reported high immunogenicity of NY-ESO-1 and suggest that a smoking-induced chronic inflammatory state might potentiate the development of NY-ESO-1-specific immune responses. Moreover, smoking might contribute to the expression of other cancer/testis antigens such as MAGE-A4 at early stages of NSCLC development.
Tracheal diverticulum is a benign cystic mass in the cervical and mediastinal regions, with an incidence of 1% in post-mortem findings, and 2% in CT findings. The lesion is in most cases completely asymptomatic and is most commonly incidentally detected during a CT examination. We present the case of a young female patient with a tracheal diverticulum who has been followed up for 8 years by pediatric pneumologist. Patient health state deteriorated and she developed stress-induced dyspnea requiring surgical resection. Moreover, we mention differential diagnosis of other mediastinal cystic lesions.
21 patients die due to cancer (mortality: 63.6%). At 12 months, progression-free survival was 33.3% in pembrolizumab and 64% in nivolumab. Conclusion: Immunotherapy brought higher survival rate to NSCLC, with good tolerability in most cases, maintaining and improving the quality of life. However, given the disparities between responses, acknowledgment of new targets and biomarkers will make the patient selection for immunotherapy more accurate.
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