Journal
CANCER IMMUNOLOGY RESEARCH
Volume 7, Issue 4, Pages 670-682Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-18-0654
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Funding
- Dutch Cancer Society [NKI 2013-5951, 10764, 10894]
- Health Holland public-private partnership grant [LSHM15036]
- Elekta [LSHM15036]
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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 tumorspecific 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.
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