Cisplatin alters antitumor immunity and synergizes with PD-1/PD-L1 inhibition in head and neck squamous cell carcinoma

Linda Tran, Clint T Allen, Roy Xiao, Ellen Moore, Ruth Davis, So Jin Park, Katie Spielbauer, Carter Van Waes, Nicole Schmitt

Research output: Contribution to journalArticle

Abstract

Head and neck squamous cell carcinoma (HNSCC) has been treated for decades with cisplatin chemotherapy, and anti–PD-1 immunotherapy has recently been approved for the treatment of this disease. However, preclinical studies of how antitumor immunity in HNSCC is affected by cisplatin alone or in combination with immunotherapies are lacking. Here, we show that sublethal doses of cisplatin may enhance antigen presentation and T-cell killing in vitro, though cisplatin also upregulates tumor cell expression of PD-L1 and may impair T-cell function at higher doses. In a syngeneic mouse model of HNSCC, concurrent use of cisplatin and anti–PD-L1/PD-1 delayed tumor growth and enhanced survival without significantly reducing the number or function of tumor-infiltrating immune cells or increasing cisplatin-induced toxicities. These results suggest that moderate doses of cisplatin may enhance antitumor immunity by mechanisms other than direct tumor cell killing, which may be further enhanced by anti–PD-L1/ PD-1 therapy.

Original languageEnglish (US)
Pages (from-to)1141-1151
Number of pages11
JournalCancer immunology research
Volume5
Issue number12
DOIs
StatePublished - Dec 1 2017

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Cisplatin
Immunity
Immunotherapy
Neoplasms
T-Lymphocytes
Antigen Presentation
Carcinoma, squamous cell of head and neck
Up-Regulation
Drug Therapy
Therapeutics
Growth

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

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Cisplatin alters antitumor immunity and synergizes with PD-1/PD-L1 inhibition in head and neck squamous cell carcinoma. / Tran, Linda; Allen, Clint T; Xiao, Roy; Moore, Ellen; Davis, Ruth; Park, So Jin; Spielbauer, Katie; Van Waes, Carter; Schmitt, Nicole.

In: Cancer immunology research, Vol. 5, No. 12, 01.12.2017, p. 1141-1151.

Research output: Contribution to journalArticle

Tran, Linda ; Allen, Clint T ; Xiao, Roy ; Moore, Ellen ; Davis, Ruth ; Park, So Jin ; Spielbauer, Katie ; Van Waes, Carter ; Schmitt, Nicole. / Cisplatin alters antitumor immunity and synergizes with PD-1/PD-L1 inhibition in head and neck squamous cell carcinoma. In: Cancer immunology research. 2017 ; Vol. 5, No. 12. pp. 1141-1151.
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