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

Clin Cancer Res. 2019 Jan 1;25(1):240-252. doi: 10.1158/1078-0432.CCR-18-1749. Epub 2018 Sep 17.

Abstract

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 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.

Conclusions: The tissue of origin significantly affects the overall shape of the immune infiltrate in primary tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53