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Clin Cancer Res

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 Höllt, Lilly-Ann van der Velden, Sylvia I. van Egmond, Kim Kortekaas, Peggy J de Vos van Steenwijk, Mariette IE van Poelgeest , Marij J P Welters, and Sjoerd H. van der Burg

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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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Saskia J Santegoets, Vanessa J van Ham, Ilina Ehsan, Pornpimol Charoentong, Chantal L Duurland, Vincent van Unen, Thomas Höllt, et al., The Anatomical Location Shapes the Immune Infiltrate in Tumors of Same Etiology and Affects Survival, Clin Cancer Res, 25, pp. 240–252, 2019.

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@article{bib:santegoets:2019,
    author       = { Santegoets, Saskia J and van Ham, Vanessa J and Ehsan, Ilina and Charoentong, Pornpimol and Duurland, Chantal L and van Unen, Vincent and Höllt, Thomas and van der Velden, Lilly-Ann and van Egmond, Sylvia I. and Kortekaas, Kim  and de Vos van Steenwijk, Peggy J and van Poelgeest , Mariette IE and Welters, Marij J P and van der Burg, Sjoerd H. },    
    title        = { The Anatomical Location Shapes the Immune Infiltrate in Tumors of Same Etiology and Affects Survival },
    journal      = { Clin Cancer Res },
    volume       = { 25 },
    year         = { 2019 },
    pages        = { 240--252 },
    doi          = { 10.1158/1078-0432.CCR-18-1749 },
    pubmedid     = { 30224343 },
    url          = { https://publications.graphics.tudelft.nl/papers/130 },
}