Journal
ORAL ONCOLOGY
Volume 95, Issue -, Pages 127-135Publisher
ELSEVIER
DOI: 10.1016/j.oraloncology.2019.06.016
Keywords
Cisplatin chemotherapy; Immunogenic cell death; Head and neck cancer; Squamous cell carcinoma
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Funding
- Intramural Research Program of the NIH, NIDCD [ZIA-DC-DC000090]
- NIH Academy Enrichment Program
- NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS [ZIADC000090] Funding Source: NIH RePORTER
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Objectives: Prior studies suggest that oxaliplatin is unique among platinum chemotherapy drugs in its ability to enhance anti-tumor immunity, but the immune mechanisms of different platinum chemotherapy drugs have not been previously compared in preclinical models of head and neck squamous cell carcinoma (HNSCC). Materials and methods: Human HNSCC cell lines were treated with cisplatin or oxaliplatin, then assessed for markers associated with immunogenic cell death (ICD) and antigen processing. A syngeneic mouse model of oral cancer was then used to compare the effects of cisplatin vs. oxaliplatin, alone or in combination with anti-PD-1 immunotherapy, on tumor growth and survival. A subset of spleens and tumors were analyzed for ICD markers and immune cell infiltrates by flow cytometry. Results: Cisplatin and oxaliplatin both increased cell surface levels of calreticulin, HSP70, MHC class I and PD-L1 in multiple cell lines. Inoculation of immunocompetent mice with cells killed in vitro by either drug resulted in failure of subsequently-injected live tumor cells to establish and grow in a small proportion of animals. Systemic cisplatin and oxaliplatin induced similar tumor growth delay when combined with anti-PD-1 therapy. Conclusions: Treatment of HNSCC cells with platinum chemotherapy appears to induce some features of antitumor immunity, which may be enhanced by anti-PD-1 therapy. Cisplatin, the standard drug for HNSCC, appears to affect anti-tumor immunity in a similar fashion to oxaliplatin in these preclinical models.
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