Radiotherapy and Cisplatin Increase Immunotherapy Efficacy by Enabling Local and Systemic Intratumoral T-cell Activity

Paula Kroon, Elselien Frijlink, Victoria Iglesias-Guimarais, Andriy Volkov, Marit M. van Buuren, Ton N. Schumacher, Marcel Verheij, Jannie Borst, Inge Verbrugge

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Abstract

To increase cancer immunotherapy success, PD-1 blockade must be combined with rationally selected treatments. Here, we examined, in a poorly immunogenic mouse breast cancer model, the potential of antibody-based immunomodulation and conventional anticancer treatments to collaborate with anti–PD-1 treatment. One requirement to improve anti-PD-1–mediated tumor control was to promote tumor-specific cytotoxic T-cell (CTL) priming, which was achieved by stimulating the CD137 costimulatory receptor. A second requirement was to overrule PD-1–unrelated mechanisms of CTL suppression in the tumor microenvironment (TME). This was achieved by radiotherapy and cisplatin treatment. In the context of CD137/PD-1–targeting immunotherapy, radiotherapy allowed for tumor elimination by altering the TME, rather than intrinsic CTL functionality. Combining this radioimmunotherapy regimen with low-dose cisplatin improved CTL-dependent regression of a contralateral tumor outside the radiation field. Thus, systemic tumor control may be achieved by combining immunotherapy protocols that promote T-cell priming with (chemo)radiation protocols that permit CTL activity in both the irradiated tumor and (occult) metastases.
Original languageEnglish
Pages (from-to)670-682
JournalCancer Immunology Research
Volume7
Issue number4
DOIs
Publication statusPublished - 1 Apr 2019
Externally publishedYes

Cite this

Kroon, P., Frijlink, E., Iglesias-Guimarais, V., Volkov, A., van Buuren, M. M., Schumacher, T. N., ... Verbrugge, I. (2019). Radiotherapy and Cisplatin Increase Immunotherapy Efficacy by Enabling Local and Systemic Intratumoral T-cell Activity. Cancer Immunology Research, 7(4), 670-682. https://doi.org/10.1158/2326-6066.CIR-18-0654