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

Saskia J. Santegoets, Vanessa J. van Ham, Ilina Ehsan, Pornpimol Charoentong, Chantal L. Duurland, Vincent van Unen, Thomas Hollt, Lilly Ann van der Velden, Sjoerd H. van der Burg*, More Authors

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

22 Citations (Scopus)


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 CD8þCD103þCD161þ effector T cells and less CD4þCD161þ effector memory T cells than OPSCC. CD161þ effector cells produced the highest cytokine levels among tumor-specific T cells. Differences in CD4þ T-cell infiltration between cervical carcinoma and OPSCC were reflected in the detection rate of intratumoral HPV-specific CD4þ 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.

Original languageEnglish
Pages (from-to)240-252
Number of pages13
JournalClinical Cancer Research
Issue number1
Publication statusPublished - 2019


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