Characterization of the tumor immune micromilieu and its interference with outcome after concurrent chemoradiation in patients with oropharyngeal carcinomas

Anne Kathrin Hess, Korinna Jöhrens, Andre Zakarneh, Panagiotis Balermpas, Jens Von Der Grün, Claus Rödel, Wilko Weichert, Michael Hummel, Ulrich Keilholz, Volker Budach, Ingeborg Tinhofer

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background: Intra-tumoral CD8 + T-cell infiltration in squamous cell carcinoma of the head and neck (HNSCC) has previously been linked to the efficacy of cisplatin-based chemoradiation (CDDP-CRTX) and immune checkpoint inhibitor (ICI) monotherapy. Further detailed characterization of the tumor immune-micromilieu and its influence on outcome may guide the development of CRTX-ICI combinations. Methods: Comprehensive immune transcriptome analysis was applied to a training set of tumor specimens from oropharyngeal squamous cell carcinoma (OPSCC) patients treated with CDDP-CRTX in the ARO-0401 phase III study (n = 33). A composite immune signature risk score (ISRS) for survival prediction was developed, and subsequently validated in two independent OPSCC cohorts treated with either CDDP-CRTX (n = 36) or mitomycin-based CRTX (MMC-CRTX, n = 31). Further validation of the ISRS was performed in the OPSCC subset (n = 79) of the TCGA HNSCC cohort. Potential interference between immune signatures and HPV status was evaluated in multivariate Cox regression models. Results: Significant differences according to the 3-y OS status in the abundance of tumor-infiltrating T- and B-cells, and the expression levels of 51 immune-related genes were observed. A risk score based on 13 differentially expressed genes involved in cytokine signaling, T-cell effector functions and the TNFR pathway was established as robust predictive factor of OS. Its predictive power was superior to the 6-gene interferon-gamma signature of ICI efficacy and independent of the HPV status. Conclusions: This study further elucidates the complex interaction of the tumor immune microenvironment with the efficacy of CDDP-CRTX in OPSCC. The results suggest immune markers for selection of patients treated with CRTX-ICI combinations.

Original languageEnglish
Article numbere1614858
JournalOncoImmunology
Volume8
Issue number8
DOIs
StatePublished - 2019

Keywords

  • Immune signature
  • head neck cancer
  • prediction score
  • prognostic biomarker
  • radiochemotherapy

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