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Publications

Journal Article Research Support, Non-U.S. Gov't Ppublish 10 citations

PubMed: 35584864 DOI: 10.1136/jitc-2021-004239

Deconvolution of malignant pleural effusions immune landscape unravels a novel macrophage signature associated with worse clinical outcome in lung adenocarcinoma patients.

J Immunother Cancer 10(5)

Authors: Sara Bruschini, Matteo Pallocca, Eleonora Sperandio, Lorenzo D'Ambrosio, Francesca Ascenzi, Claudia De Vitis, Valentina Salvati, Antonella Esposito, Simona Di Martino, Francesca De Nicola, Francesca Paolini, Luigi Fattore, Gabriele Alessandrini, Francesco Facciolo, Maria Laura Foddai, Massimiliano Bassi, Federico Venuta, Michela D'Ascanio, Alberto Ricci, Antonio D' Andrilli, Christian Napoli, Luigi Aurisicchio, Maurizio Fanciulli, Erino Angelo Rendina, Gennaro Ciliberto, Rita Mancini

Affiliations

  • Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy.
  • Department Clinical and Molecular Medicine, Sant' Andrea Hospital-Sapienza University of Rome, Rome, Italy.
  • Biostatistics, Bioinformatics and Clinical Trial Center, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • Tumor Immunology and Immunotherapy Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • Department of Clinical and Molecular Medicine, Sant' Andrea Hospital-Sapienza University of Rome, Rome, Italy.
  • Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • Pathology Unit, IRCCS-Regina Elena National Cancer Institute, Rome, Italy.
  • SAFU Laboratory, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • HPV-Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • Thoracic Surgery Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • Immunohematology and Transfusional Medicine Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • Thoracic Surgery Unit, Sapienza University of Rome, Rome, Italy.
  • Thoracic Surgery Unit, Sant' Andrea Hospital-Sapienza University of Rome, Rome, Italy.
  • Department of Medical Surgical Sciences and Translational Medicine, Sapienza University of Rome, Rome, Italy.
  • Takis Srl, Roma, Italy.
  • Scientific Directorate, IRCSS Regina Elena National Cancer Institute, Rome, Italy.

Abstract

BACKGROUND

Immune checkpoint inhibitors are still unable to provide clinical benefit to the large majority of non-small cell lung cancer (NSCLC) patients. A deeper characterization of the tumor immune microenvironment (TIME) is expected to shed light on the mechanisms of cancer immune evasion and resistance to immunotherapy. Here, we exploited malignant pleural effusions (MPEs) from lung adenocarcinoma (LUAD) patients as a model system to decipher TIME in metastatic NSCLC.

METHODS

Mononuclear cells from MPEs (PEMC) and peripheral blood (PBMC), cell free pleural fluid and/or plasma were collected from a total of 24 LUAD patients and 12 healthy donors. Bulk-RNA sequencing was performed on total RNA extracted from PEMC and matched PBMC. The DEseq2 Bioconductor package was used to perform differential expression analysis and CIBERSORTx for the regression-based immune deconvolution of bulk gene expression data. Cytokinome analysis of cell-free pleural fluid and plasma samples was performed using a 48-Plex Assay panel. THP-1 monocytic cells were used to assess macrophage polarization. Survival analyses on NSCLC patients were performed using KM Plotter (LUAD, N=672; lung squamous cell carcinoma, N=271).

RESULTS

Transcriptomic analysis of immune cells and cytokinome analysis of soluble factors in the pleural fluid depicted MPEs as a metastatic niche in which all the components required for an effective antitumor response are present, but conscripted in a wound-healing, proinflammatory and tumor-supportive mode. The bioinformatic deconvolution analysis revealed an immune landscape dominated by myeloid subsets with the prevalence of monocytes, protumoral macrophages and activated mast cells. Focusing on macrophages we identified an MPEs-distinctive signature associated with worse clinical outcome in LUAD patients.

CONCLUSIONS

Our study reports for the first time a wide characterization of MPEs LUAD microenvironment, highlighting the importance of specific components of the myeloid compartment and opens new perspectives for the rational design of new therapies for metastatic NSCLC.

MeSH

Cells, Lung, Pleural Effusion, Tumor Escape, Macrophages, Neoplasms, Adenocarcinoma, Carcinoma, Non-Small-Cell Lung, Adenocarcinoma Of Lung, Immunotherapy, Lung Neoplasms, Tumor Microenvironment, Computational Biology, Plasma, Pleural Effusion, Malignant

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