AUTHOR=Erreni Marco , Fumagalli Maria Rita , Marozzi Matteo , Leone Roberto , Parente Raffaella , D’Anna Raffaella , Doni Andrea TITLE=From surfing to diving into the tumor microenvironment through multiparametric imaging mass cytometry JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1544844 DOI=10.3389/fimmu.2025.1544844 ISSN=1664-3224 ABSTRACT=The tumor microenvironment (TME) is a complex ecosystem where malignant and non-malignant cells cooperate and interact determining cancer progression. Cell abundance, phenotype and localization within the TME vary over tumor development and in response to therapeutic interventions. Therefore, increasing our knowledge of the spatiotemporal changes in the tumor ecosystem architecture is of importance to better understand the etiologic development of the neoplastic diseases. Imaging Mass Cytometry (IMC) represents the elective multiplexed imaging technology enabling the in-situ analysis of up to 43 different protein markers for in-depth phenotypic and spatial investigation of cells in their preserved microenvironment. IMC is currently applied in cancer research to define the composition of the cellular landscape and to identify biomarkers of predictive and prognostic significance with relevance in mechanisms of drug resistance. Herein, we describe the general principles and experimental workflow of IMC raising the informative potential in preclinical and clinical cancer research.