Cisplatin and oxaliplatin induce similar immunogenic changes in preclinical models of head and neck cancer

Oral Oncol. 2019 Aug:95:127-135. doi: 10.1016/j.oraloncology.2019.06.016. Epub 2019 Jun 20.

Abstract

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 anti-tumor 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.

Keywords: Cisplatin chemotherapy; Head and neck cancer; Immunogenic cell death; Squamous cell carcinoma.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antigen Presentation / drug effects
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Cell Line, Tumor / transplantation
  • Cisplatin / pharmacology*
  • Cisplatin / therapeutic use
  • Disease Models, Animal
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Female
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / pathology
  • Humans
  • Mice
  • Oxaliplatin / pharmacology*
  • Oxaliplatin / therapeutic use
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology
  • Squamous Cell Carcinoma of Head and Neck / drug therapy*
  • Squamous Cell Carcinoma of Head and Neck / immunology
  • Squamous Cell Carcinoma of Head and Neck / pathology

Substances

  • Antineoplastic Agents, Immunological
  • PDCD1 protein, human
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor
  • Oxaliplatin
  • Cisplatin