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Integrating AI-Powered Digital Pathology and Imaging Mass Cytometry Identifies Key Classifiers of Tumor Cells, Stroma, and Immune Cells in Non-Small Cell Lung Cancer.
Rigamonti, Alessandra; Viatore, Marika; Polidori, Rebecca; Rahal, Daoud; Erreni, Marco; Fumagalli, Maria Rita; Zanini, Damiano; Doni, Andrea; Putignano, Anna Rita; Bossi, Paola; Voulaz, Emanuele; Alloisio, Marco; Rossi, Sabrina; Zucali, Paolo Andrea; Santoro, Armando; Balzano, Vittoria; Nisticò, Paola; Feuerhake, Friedrich; Mantovani, Alberto; Locati, Massimo; Marchesi, Federica.
Afiliação
  • Rigamonti A; Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital; Rozzano (Milan), Italy.
  • Viatore M; Department of Medical Biotechnology and Translational Medicine, University of Milan; Milan, Italy.
  • Polidori R; Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital; Rozzano (Milan), Italy.
  • Rahal D; Department of Medical Biotechnology and Translational Medicine, University of Milan; Milan, Italy.
  • Erreni M; Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital; Rozzano (Milan), Italy.
  • Fumagalli MR; Department of Medical Biotechnology and Translational Medicine, University of Milan; Milan, Italy.
  • Zanini D; Department of Pathology, IRCCS Humanitas Research Hospital; Rozzano (Milan), Italy.
  • Doni A; Unit of Advanced Optical Microscopy, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
  • Putignano AR; Department of Biomedical Science, Humanitas University, Pieve Emanuele, Milan, Italy.
  • Bossi P; Unit of Advanced Optical Microscopy, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
  • Voulaz E; Unit of Advanced Optical Microscopy, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
  • Alloisio M; Unit of Advanced Optical Microscopy, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
  • Rossi S; Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital; Rozzano (Milan), Italy.
  • Zucali PA; Department of Pathology, IRCCS Humanitas Research Hospital; Rozzano (Milan), Italy.
  • Santoro A; Department of Biomedical Science, Humanitas University, Pieve Emanuele, Milan, Italy.
  • Balzano V; Division of Thoracic Surgery, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy.
  • Nisticò P; Division of Thoracic Surgery, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy.
  • Feuerhake F; Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy.
  • Mantovani A; Department of Biomedical Science, Humanitas University, Pieve Emanuele, Milan, Italy.
  • Locati M; Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy.
  • Marchesi F; Department of Biomedical Science, Humanitas University, Pieve Emanuele, Milan, Italy.
Cancer Res ; 84(7): 1165-1177, 2024 Apr 01.
Article em En | MEDLINE | ID: mdl-38315789
ABSTRACT
Artificial intelligence (AI)-powered approaches are becoming increasingly used as histopathologic tools to extract subvisual features and improve diagnostic workflows. On the other hand, hi-plex approaches are widely adopted to analyze the immune ecosystem in tumor specimens. Here, we aimed at combining AI-aided histopathology and imaging mass cytometry (IMC) to analyze the ecosystem of non-small cell lung cancer (NSCLC). An AI-based approach was used on hematoxylin and eosin (H&E) sections from 158 NSCLC specimens to accurately identify tumor cells, both adenocarcinoma and squamous carcinoma cells, and to generate a classifier of tumor cell spatial clustering. Consecutive tissue sections were stained with metal-labeled antibodies and processed through the IMC workflow, allowing quantitative detection of 24 markers related to tumor cells, tissue architecture, CD45+ myeloid and lymphoid cells, and immune activation. IMC identified 11 macrophage clusters that mainly localized in the stroma, except for S100A8+ cells, which infiltrated tumor nests. T cells were preferentially localized in peritumor areas or in tumor nests, the latter being associated with better prognosis, and they were more abundant in highly clustered tumors. Integrated tumor and immune classifiers were validated as prognostic on whole slides. In conclusion, integration of AI-powered H&E and multiparametric IMC allows investigation of spatial patterns and reveals tissue relevant features with clinical relevance.

SIGNIFICANCE:

Leveraging artificial intelligence-powered H&E analysis integrated with hi-plex imaging mass cytometry provides insights into the tumor ecosystem and can translate tumor features into classifiers to predict prognosis, genotype, and therapy response.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Limite: Humans Idioma: En Revista: Cancer Res Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Limite: Humans Idioma: En Revista: Cancer Res Ano de publicação: 2024 Tipo de documento: Article