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

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2019-07, Vol.68 (7), p.1133-1141
• Main Authors: Ludwig, Sonja, Hong, Chang-Sook, Razzo, Beatrice M., Fabian, Kellsye P. L., Chelvanambi, Manoj, Lang, Stephan, Storkus, Walter J., Whiteside, Theresa L.
• Format: Article
• Language: English
• Subjects: 4-Nitroquinoline-1-oxide - toxicity; Animals; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer Research; Cancer Vaccines - therapeutic use; CD8 antigen; Chemotherapy; Cisplatin; Cisplatin - therapeutic use; Combined Modality Therapy - methods; Combined vaccines; Epitopes; Female; Immunology; Immunoregulation; Immunotherapy - methods; Lymphocytes T; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Mouth Neoplasms - chemically induced; Mouth Neoplasms - immunology; Mouth Neoplasms - pathology; Mouth Neoplasms - therapy; Neoplasms, Experimental - chemically induced; Neoplasms, Experimental - immunology; Neoplasms, Experimental - pathology; Neoplasms, Experimental - therapy; Oncology; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; Original Article; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - chemically induced; Squamous Cell Carcinoma of Head and Neck - immunology; Squamous Cell Carcinoma of Head and Neck - pathology; Squamous Cell Carcinoma of Head and Neck - therapy; Treatment Outcome; Triazines - therapeutic use; Triazoles - therapeutic use; Vaccines, Subunit - therapeutic use
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-019-02348-2

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 A 2A R 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.