LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

Abstract 1349: Exploring CD63 as a targetable mediator of the pro-tumorigenic tissue microenvironment in HNSCC

Photo from wikipedia

Introduction: Head and neck squamous cell carcinoma (HNSCC) is one of the ten most common cancer types worldwide - ranked on the sixth position with 560,000 new diagnoses and 270,000… Click to show full abstract

Introduction: Head and neck squamous cell carcinoma (HNSCC) is one of the ten most common cancer types worldwide - ranked on the sixth position with 560,000 new diagnoses and 270,000 deaths in 2020. The survival could be increased only slightly over the past decades and in addition the incidence of HNSCC continues to rise. In this study, we investigated the role of the tetraspanin CD63 during cancer progression. Methods: First, we performed survival analyses with available statistics from data bases to correlate CD63 and survival. Then, we established a 20-marker spectral FACS panel to identify different fibroblast subpopulations in patient tissue. Upon receiving patient consent, fresh HNSCC tissue was received from surgical tumor resections at the University Hospital of Bonn. We mechanically and enzymatically digested and purified the tissue of ten patients to create single-cell suspensions. After staining, the cells were measured on a Sony ID7000 Spectral Analyzer and interpreted with FlowJo. To identify whether CD63 on fibroblasts affects the differentiation of macrophages in vitro, we isolated primary fibroblasts and monocytes from HNSCC patients and deleted CD63 in fibroblasts by CRISPR-Cas9. Thereafter, we co-incubated fibroblasts (without and with the CD63-Knockout) and macrophages over ten days in M-CSF containing medium, and measured the expression of M1 and M2 markers through flow cytometry. Results: First, correlating CD63 gene expression with the patient outcome showed that CD63 correlated with a decreased survival. Then, analyzing fresh tumor specimens with the multicolor panel showed an increase of CD63 expression in different fibroblast subpopulations in the tumor specimens, e. g. CD9+ CD34+ CD63+ CD90+ fibroblasts increased more than eightfold. Investigating potential mechanisms, by which CD63 expression on fibroblasts affects tumor progression, deleting CD63 steered macrophages towards the pro-inflammatory M1 phenotype. Conclusion: This study demonstrates that HNSCC increases CD63 expression in different fibroblast populations and that deleting CD63 on fibroblasts can steer macrophages towards the pro-inflammatory phenotype, thereby suggesting a rationale for testing CD63 as a therapeutic target. Citation Format: Elisabeth B. Dingendorf, Michael C. Stoffel, Dahlia L. Kittel, Glen Kristiansen, Tristan Lerbs. Exploring CD63 as a targetable mediator of the pro-tumorigenic tissue microenvironment in HNSCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1349.

Keywords: cd63; expression; hnscc; exploring cd63; cancer; tissue

Journal Title: Cancer Research
Year Published: 2023

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.