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


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.

SUBMITTER: Hess AK 

PROVIDER: S-EPMC6682352 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Hess Anne-Kathrin AK   Jöhrens Korinna K   Zakarneh Andre A   Balermpas Panagiotis P   Von Der Grün Jens J   Rödel Claus C   Weichert Wilko W   Hummel Michael M   Keilholz Ulrich U   Budach Volker V   Tinhofer Ingeborg I  

Oncoimmunology 20190525 8


<h4>Background</h4>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.<h4>Methods</h4>Comprehensive immune transcriptome analysis was applied to a training set of tumor  ...[more]

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