The Anatomical Location Shapes the Immune Infiltrate in Tumors of Same Etiology and Affects Survival

The tumor immune microenvironment determines clinical outcome. Whether the original tissue in which a primary tumor develops influences this microenvironment is not well understood. We applied high-dimensional single-cell mass cytometry [Cytometry by Time-Of-Flight (CyTOF)] analysis and functional s...

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Bibliographic Details
Published in:Clinical cancer research 2019-01, Vol.25 (1), p.240-252
Main Authors: Santegoets, Saskia J, van Ham, Vanessa J, Ehsan, Ilina, Charoentong, Pornpimol, Duurland, Chantal L, van Unen, Vincent, Höllt, Thomas, van der Velden, Lilly-Ann, van Egmond, Sylvia L, Kortekaas, Kim E, de Vos van Steenwijk, Peggy J, van Poelgeest, Mariëtte I E, Welters, Marij J P, van der Burg, Sjoerd H
Format: Article
Language:English
Subjects:
Carcinoma, Squamous Cell - pathology
Carcinoma, Squamous Cell - virology
Female
Flow Cytometry
Head and Neck Neoplasms - pathology
Head and Neck Neoplasms - virology
Human papillomavirus 16 - pathogenicity
Humans
Leukocytes, Mononuclear - virology
Papillomavirus Infections - pathology
Papillomavirus Infections - virology
Prognosis
Single-Cell Analysis
T-Lymphocytes - pathology
T-Lymphocytes - virology
Tumor Microenvironment - immunology
Tumor Suppressor Protein p53 - genetics
Uterine Cervical Neoplasms - pathology
Uterine Cervical Neoplasms - virology
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Summary:The tumor immune microenvironment determines clinical outcome. Whether the original tissue in which a primary tumor develops influences this microenvironment is not well understood. 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). 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. The tissue of origin significantly affects the overall shape of the immune infiltrate in primary tumors.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-18-1749