Project description:To explore the expression pattern of circular RNAs (circRNAs) and their biological functions in malignant pleural effusion, we surveyed the circRNA expression profiles of 3 lung adenocarcinoma-associated malignant pleural effusion (LA-MPE) and 3 tuberculous pleural effusion (TPE) from clinical patients using Clariom D human microarray.
Project description:A four-dimensional independent data acquisition (4D-DIA) proteomic was performed to determine the differentially expressed proteins in pleural effusion samples collected from ung adenocarcinoma MPE, BPE (tuberculosis pleural effusion (TPE) and parapneumonic effusion (PPE)).
Project description:Interventions: Multicenter, single-arm, open-label trial
Primary outcome(s): The pleural effusion control rate (30days after administration of hypotonic cisplatin for malignant pleural effusion)
Study Design: Single arm Non-randomized
Project description:Malignant pleural effusion (MPE) is indicative of terminal malignancy with uniformly fatal prognosis. Often, two distinct compartments of tumor microenvironment, the effusion and disseminated pleural tumors, co-exist in the pleural cavity, presenting a major challenge for therapeutic interventions and drug delivery. Clinical evidence suggests that MPE comprises abundant tumor associated myeloid cells with the tumor-promoting phenotype, impairing antitumor immunity. Here, we developed liposomal cyclic dinucleotide (LNP-CDN) for targeted activation of STING signaling in macrophages and dendritic cells and showed that, upon intrapleural administration, they induce drastic changes in the transcriptional landscape in MPE, mitigating the immune cold MPE in both the effusion and pleural tumors. Moreover, combination immunotherapy with blockade of PD-L1 potently reduced MPE volume and inhibited tumor growth not only in pleural cavity but also in lung parenchyma, conferring significantly prolonged survival of MPE-bearing mice. Furthermore, the LNP-CDN-induced immunological effects were also observed with clinical MPE samples, suggesting the potential of intrapleural LNP-CDN for clinical MPE immunotherapy.
Project description:Malignant pleural effusion (MPE) is indicative of terminal malignancy with uniformly fatal prognosis. Often, two distinct compartments of tumor microenvironment, the effusion and disseminated pleural tumors, co-exist in the pleural cavity, presenting a major challenge for therapeutic interventions and drug delivery. Clinical evidence suggests that MPE comprises abundant tumor associated myeloid cells with the tumor-promoting phenotype, impairing antitumor immunity. Here, we developed liposomal cyclic dinucleotide (LNP-CDN) for targeted activation of STING signaling in macrophages and dendritic cells and showed that, upon intrapleural administration, they induce drastic changes in the transcriptional landscape in MPE, mitigating the immune cold MPE in both the effusion and pleural tumors. Moreover, combination immunotherapy with blockade of PD-L1 potently reduced MPE volume and inhibited tumor growth not only in pleural cavity but also in lung parenchyma, conferring significantly prolonged survival of MPE-bearing mice. Furthermore, the LNP-CDN-induced immunological effects were also observed with clinical MPE samples, suggesting the potential of intrapleural LNP-CDN for clinical MPE immunotherapy.
Project description:We performed a cytoscanHD array to analyze copy number variations in the genome of 33 human pleural mesothelioma cell lines established from patient pleural effusion. We were particularly interested in the analysis of the p21.3 region of chromosome 9 which contains CDKN2A tumor suppressor genes and the gene encoding type I interferons that are often deleted and confer sensitivity to oncolytic Measles virus
Project description:Soluble HLA (sHLA) molecules released to the plasma, carry their original peptide cargo and provide insight into the protein synthesis and degradation schemes of their source cells and tissues. Other body fluids, such as pleural effusions, may also contain sHLA-peptide complexes, and can potentially serve as a source of tumor antigens since these fluids are drained from the tumor microenvironment. Thus, we developed a methodology for purifying and analysing large pleural effusion sHLA class I peptidomes of patients inflicted with malignancies or benign diseases. The cleared pleural fluids, the cell pellets present in the pleural effusions, and the primary tumor cells cultured from cancer patients’ effusions, were used for immunoaffinity purification of the HLA molecules. The recovered HLA peptides were analyzed by capillary chromatography coupled to tandem mass spectrometry and the resulting LC-MS/MS data was analyzed with the MaxQuant software tool. Large HLA peptidomes were obtained by the analysis of the pleural effusions. The majority of peptides identified from the pleural effusions were defined as HLA ligands that fit the patients’ HLA consensus sequence motifs. The membranal and soluble HLA peptidomes of each individual patient were somewhat similar to each other. Many of the HLA peptides were derived from known tumor-associated antigens, lung-related proteins, and VEGF pathway proteins. Thus, the pleural effusion HLA peptidome of patients with malignant tumors can serve as a rich source of biomarkers for tumor diagnosis and personalized immunotherapy.
Project description:We profiled the exosomal circRNA in lung adenocarcinoma-associated malignant (LA-MPE) and tuberculous (TPE) pleural effusion samples by circRNA microarray to determine the potential functions and diagnostic value of the differential expressed circRNAs (DECs)