Krupar, Rosemarie and Robold, Katharina and Gaag, Doris and Spanier, Gerrit and Kreutz, Marina and Renner, Kathrin and Hellerbrand, Claus and Hofstaedter, Ferdinand and Bosserhoff, Anja K. (2014) Immunologic and metabolic characteristics of HPV-negative and HPV-positive head and neck squamous cell carcinomas are strikingly different. VIRCHOWS ARCHIV, 465 (3). pp. 299-312. ISSN 0945-6317, 1432-2307
Full text not available from this repository. (Request a copy)Abstract
An HPV infection is involved in the etiology of about 25 % of head and neck squamous cell carcinomas (HNSCC). It has been postulated that a strong antitumoral immune response in HPV-positive tumors represents an important underlying mechanism for their good response to therapy. Recently, the Warburg phenomenon has returned to the center of attention because it affects antitumoral immune response and response to therapy. Accumulation of tumor cell-derived lactate inhibits cytotoxic T cells, as these, analogous to cancer cells, depend on glycolysis and lactate secretion for fulfillment of energy needs. Sparse information exists on the Warburg effect in HNSCC. This study aimed to characterize the metabolic and immunological features of HPV-negative and HPV-positive HNSCC. An immunohistochemical analysis of oropharyngeal carcinomas showed an enhanced antitumoral immune response (CD8/CD4 ratio) together with increased levels of proteins involved in transmembranous metabolite transportation (GLUT1 and CD147) and respiratory metabolism (COX5B) in HPV-positive tumors as compared to HPV-negative tumors. mRNA and Western blot analyses of an HPV-positive and HPV-negative HNSCC cell line revealed metabolic characteristics similar to the in vivo situation. Additionally, the HPV-negative cell line showed stronger extracellular lactate accumulation. In contrast, the HPV-positive cell line presented with better adaption to lactic acidosis suggesting an ability to metabolize lactate. Our results indicate that HPV-positive and HPV-negative carcinomas do not only differ in terms of tumor immune microenvironment, but also in terms of tumor metabolism, characterized by an increased glucose and respiratory metabolism together with decreased lactate accumulation in HPV-positive HNSCC. Therefore, targeting metabolic pathways could represent a promising adjunct in the therapy of HPV-positive HNSCC.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HIGH LACTATE LEVELS; HUMAN-PAPILLOMAVIRUS; TUMOR RECURRENCE; RISK-FACTOR; CANCER; SURVIVAL; INFILTRATION; EXPRESSION; INFECTION; MARKERS; Head and neck squamous cell carcinoma (HNSCC); Human papillomavirus (HPV); Tumor metabolism; Tumor infiltrating lymphocytes; Tumor microenvironment; Warburg effect |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Aug 2019 11:02 |
| Last Modified: | 29 Aug 2019 11:02 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9675 |
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