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Decoding Immune Heterogeneity of Triple Negative Breast Cancer and Its Association with Systemic Inflammation

1
Biochemistry Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
2
Molecular Targeting Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
3
Analytical Epidemiology and Health Impact Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
4
Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, 20133 Milan, Italy
5
Pathological Anatomy Unit, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
6
Division of Surgical Oncology, Breast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(7), 911; https://doi.org/10.3390/cancers11070911
Received: 7 May 2019 / Revised: 21 June 2019 / Accepted: 25 June 2019 / Published: 28 June 2019
(This article belongs to the Special Issue Inflammation and Cancer Metastasis)
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Abstract

Triple negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options. New opportunities are emerging from current comprehensive characterization of tumor immune infiltration and fitness. Therefore, effectiveness of current chemotherapies and novel immunotherapies are partially dictated by host inflammatory and immune profiles. However, further progress in breast cancer immuno-oncology is required to reach a detailed awareness of the immune infiltrate landscape and to determine additional reliable and easily detectable biomarkers. In this study, by analyzing gene expression profiles of 54 TNBC cases we identified three TNBC clusters displaying unique immune features. Deep molecular characterization of immune cells cytolytic-activity and tumor-inflammation status reveled variability in the local composition of the immune infiltrate in the TNBC clusters, reconciled by tumor-infiltrating lymphocytes counts. Platelet-to-lymphocyte ratio (PLR), a blood systemic parameter of inflammation evaluated using pre-surgical blood test data, resulted negatively correlated with local tumoral cytolytic activity and T cell–inflamed microenvironment, whereas tumor aggressiveness score signature positively correlated with PLR values. These data highlighted that systemic inflammation parameters may represent reliable and informative markers of the local immune tumor microenvironment in TNBC patients and could be exploited to decipher tumor infiltrate properties and consequently to select the most appropriate therapies. View Full-Text
Keywords: TNBC; immune heterogeneity; TILs; inflammation; PLR; platelet; CBC TNBC; immune heterogeneity; TILs; inflammation; PLR; platelet; CBC
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Romero-Cordoba, S.; Meneghini, E.; Sant, M.; Iorio, M.V.; Sfondrini, L.; Paolini, B.; Agresti, R.; Tagliabue, E.; Bianchi, F. Decoding Immune Heterogeneity of Triple Negative Breast Cancer and Its Association with Systemic Inflammation. Cancers 2019, 11, 911.

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