2. Academic Validation
  3. Impact of combination immunochemotherapies on progression of 4NQO-induced murine oral squamous cell carcinoma

Impact of combination immunochemotherapies on progression of 4NQO-induced murine oral squamous cell carcinoma

  • Cancer Immunol Immunother. 2019 Jul;68(7):1133-1141. doi: 10.1007/s00262-019-02348-2.
Sonja Ludwig 1 2,  Chang-Sook Hong 2 3,  Beatrice M Razzo 2,  Kellsye P L Fabian 4,  Manoj Chelvanambi 4,  Stephan Lang 1,  Walter J Storkus 2 4 5,  Theresa L Whiteside 6 7 8 9
Affiliations

Affiliations

  • 1 Department of Otorhinolaryngology and Head and Surgery, University Hospital Essen, Essen, Germany.
  • 2 University of Pittsburgh, Medical Center (UPMC), Hillman Cancer Center, Suite 1.32b, 5117 Centre Ave, Pittsburgh, PA, 15213, USA.
  • 3 Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.
  • 4 Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.
  • 5 Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.
  • 6 University of Pittsburgh, Medical Center (UPMC), Hillman Cancer Center, Suite 1.32b, 5117 Centre Ave, Pittsburgh, PA, 15213, USA. whitesidetl@upmc.edu.
  • 7 Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA. whitesidetl@upmc.edu.
  • 8 Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA. whitesidetl@upmc.edu.
  • 9 Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA. whitesidetl@upmc.edu.
PMID: 31139925 DOI: 10.1007/s00262-019-02348-2
Abstract

Advanced oral squamous cell carcinomas (OSCC) have limited therapeutic options. Although immune therapies are emerging as a potentially effective alternative or adjunct to chemotherapies, the therapeutic efficacy of combination immune chemotherapies has yet to be determined. Using a 4-nitroquinolone-N-oxide (4NQO) orthotopic model of OSCC in immunocompetent mice, we evaluated the therapeutic efficacy of single- and combined-agent treatment with a poly-epitope tumor peptide vaccine, cisplatin and/or an A2AR inhibitor, ZM241385. The monotherapies or their combinations resulted in a partial inhibition of tumor growth and, in some cases, a significant but transient upregulation of systemic anti-tumor CD8+ T cell responses. These responses eroded in the face of expanding immunoregulatory cell populations at later stages of tumor progression. Our findings support the need for the further development of combinatorial therapeutic approaches that could more effectively silence dominant immune inhibitory pathways operating in OSCC and provide novel, more beneficial treatment options for this tumor.

Keywords

4NQO model; A2AR inhibition; Carcinogenesis; Chemotherapy; Oral squamous cell carcinoma; Vaccination.

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