Adenocarcinoma of the Uterine Cervix Shows Impaired Recruitment of cDC1 and CD8+ T Cells and Elevated β-Catenin Activation Compared with Squamous Cell Carcinoma

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Abstract

PURPOSE: Adenocarcinoma (AC) of the uterine cervix is the second most common type of cervical cancer after squamous cell carcinoma (SCC). Although both subtypes are treated similarly, patients with AC have a worse prognosis. In this study, immunologic features of the tumor microenvironment in these two subsets were pursued with potential therapeutic implications.

EXPERIMENTAL DESIGN: The immune microenvironment of primary tumors (PT) and non-metastatic tumor-draining lymph nodes (TDLN) was compared between patients with cervical AC (n = 16) and SCC (n = 20) by polychromatic flow cytometry and by transcriptional profiling of the PT (n = 299) using publicly available data from The Cancer Genome Atlas (TCGA).

RESULTS: Flowcytometric analyses revealed intact T-cell differentiation in TDLN but hampered effector T-cell trafficking to the PT in AC, as compared to SCC. TCGA analysis demonstrated higher expression of chemokines involved in effector T-cell homing (CXCL9/10/11) in SCC PT as compared to AC PT, which was highly correlated to a transcriptional signature for type 1 conventional dendritic cells (cDC1). This was consistent with elevated frequencies of CD141+/BDCA3+ cDC1 in PT SCC samples relative to AC and correspondingly elevated levels of CXCL9 and CXCL10 in 24h ex-vivo cultures. Hampered cDC1 recruitment in AC was in turn related to lower transcript levels of cDC1-recruiting chemokines and an elevated β-catenin activation score, and was associated with poor overall survival.

CONCLUSIONS: Our data have identified an opportunity for the investigation of potentially novel therapeutic interventions in AC of the cervix, i.e. β-catenin inhibition and cDC1 mobilization.

Original languageEnglish
Number of pages12
JournalClinical Cancer Research
Volume26
Issue number14
DOIs
Publication statusE-pub ahead of print - 27 Mar 2020

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