The anatomical location shapes the immune infiltrate in tumors of same etiology and affects survival

Purpose: The tumor immune microenvironment determines clinical outcome. Whether the original tissue in which a primary tumor develops influences this microenvironment is not well understood. - Experimental Design: We applied high-dimensional single-cell mass cytometry [Cytometry by Time-Of-Flight (C...

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Main Authors: Santegoets, Saskia J. A. M. (Author) , Charoentong, Pornpimol (Author)
Format: Article (Journal)
Language:English
Published: 2019
In: Clinical cancer research
Year: 2018, Volume: 25, Issue: 1, Pages: 240-252
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-18-1749
Online Access:Verlag, Volltext: https://doi.org/10.1158/1078-0432.CCR-18-1749
Verlag, Volltext: http://clincancerres.aacrjournals.org/content/25/1/240
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Author Notes:Saskia J. Santegoets, Vanessa J. van Ham, Ilina Ehsan, Pornpimol Charoentong, Chantal L. Duurland, Vincent van Unen, Thomas Höllt, Lilly-Ann van der Velden, Sylvia L. van Egmond, Kim E. Kortekaas, Peggy J. de Vos van Steenwijk, Mariëtte I.E. van Poelgeest, Marij J.P. Welters, and Sjoerd H. van der Burg

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520 |a Purpose: The tumor immune microenvironment determines clinical outcome. Whether the original tissue in which a primary tumor develops influences this microenvironment is not well understood. - Experimental Design: We applied high-dimensional single-cell mass cytometry [Cytometry by Time-Of-Flight (CyTOF)] analysis and functional studies to analyze immune cell populations in human papillomavirus (HPV)-induced primary tumors of the cervix (cervical carcinoma) and oropharynx (oropharyngeal squamous cell carcinoma, OPSCC). - Results: Despite the same etiology of these tumors, the composition and functionality of their lymphocytic infiltrate substantially differed. Cervical carcinoma displayed a 3-fold lower CD4:CD8 ratio and contained more activated CD8+CD103+CD161+ effector T cells and less CD4+CD161+ effector memory T cells than OPSCC. CD161+ effector cells produced the highest cytokine levels among tumor-specific T cells. Differences in CD4+ T-cell infiltration between cervical carcinoma and OPSCC were reflected in the detection rate of intratumoral HPV-specific CD4+ T cells and in their impact on OPSCC and cervical carcinoma survival. The peripheral blood mononuclear cell composition of these patients, however, was similar. - Conclusions: The tissue of origin significantly affects the overall shape of the immune infiltrate in primary tumors. 
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