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.

@Article { SVECDVHVVKDVWV19,
  author       = "Santegoets, Saskia J and Ham, Vanessa J van and Ehsan, Ilina and Charoentong, Pornpimol and Duurland, Chantal
                  L and Unen, Vincent van and H\öllt, Thomas and Velden, Lilly-Ann van der and Egmond, Sylvia I. van and
                  Kortekaas, Kim  and Vos van Steenwijk, Peggy J de and Poelgeest , Mariette IE van 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 Impacts Survival",
  journal      = "Clinical Cancer Research",
  number       = "1",
  volume       = "25",
  month        = "jan",
  year         = "2019",
  note         = "DOI: 10.1158/1078-0432.CCR-18-1749",
  url          = "http://graphics.tudelft.nl/Publications-new/2019/SVECDVHVVKDVWV19"
}