Assessment of the impact of low dose solid tumor irradiation on tumor growth, metastases, immune cell activation, and subsequent immunotherapy in a humanized tumor mouse model

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There is mounting evidence that tumor irradiation can be applied in a combination with immunotherapy using certain fractionation and dosing schedules to elicit immunogenic anti-tumor activity within the treated primary solid tumor. Verifiably, tumor irradiation causes an enhanced upregulation of major histocompatibility complex (MHC) class I expression, the release of chemokines, and enhanced presentation of tumor associated epitopes. Moreover, the combination of radiation and an anti-immune checkpoint treatment can trigger a potent enough immune response that in some cases may shrink metastatic tumors outside of the radiation field. Exploiting synergistic effects by using the radiated primary tumor as an antigen source to provoke a potent systemic antitumor response augmented by immunomodulators would be an intriguing treatment approach for neoadjuvant or de-novo metastatic breast cancer patients. However, radiotherapy is not usually considered in the context of neoadjuvant therapy for breast cancer. Unlike esophageal, rectal or anal cancer, preoperative radiotherapy has been little studied in breast cancer yet. Here we aim to systematically evaluate the effect of bulk tumor irradiation on the inherent immunological tumor defense and on subsequent immune-checkpoint (anti-PD-L1) targeting in a human-like mouse model using so called humanized tumor mice.