The Anatomical Location Shapes the Immune Infiltrate in Tumors of Same Etiology and Impacts 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 (CyTOF) analysis and functional studies to analyze immune cell populations in human papillomavirus (HPV)-induced primary tumors of the cervix (CxCa) and oropharynx (OPSCC). Results: Despite the same etiology of these tumors, the composition and functionality of their lymphocytic infiltrate substantially differed. CxCa displayed a 3-fold lower CD4:CD8 ratio, 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 CxCa and OPSCC were reflected in the detection rate of intratumoral HPV-specific CD4+ T-cells and in their impact on OPSCC and CxCa survival. The PBMC composition of these patients, however, was similar. Conclusions: The tissue of origin significantly impacts the overall shape of the immune infiltrate in primary tumors.

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@article{ bib:2018_clinical_cancer_research,
    author = {Saskia J Santegoets and Vanessa J van Ham and Ilina Ehsan and Pornpimol Charoentong and Chantal L Duurland and Vincent van Unen and Thomas H{\"o}llt and Lilly-Ann van der Velden and Sylvia I van Egmond and Kim Kortekaas and Peggy J de Vos van Steenwijk and Mariette IE van Poelgeest and Marij J P Welters and Sjoerd H van der Burg},
    title = { The Anatomical Location Shapes the Immune Infiltrate in Tumors of Same Etiology and Impacts Survival },
    journal = { Clinical Cancer Research },
    volume = { 25 },
    number = { 1 },
    year = { 2019 },
    doi = { 10.1158/1078-0432.CCR-18-1749 },
}