Improving immunotherapy for breast cancer patients

Abstract

In this thesis, we aimed to explore short-term immune induction treatments to prime breast tumors for immunotherapy response and to investigate immune responses in breast cancer for improved patient selection. In the TONIC-trial, a two-week induction treatment with low-dose chemotherapy or irradiation, most notably doxorubicin or cisplatin, followed by immunotherapy was able to induce clinical and immunological responses in patients with metastatic triple-negative breast cancer (no expression of the hormone receptor; TNBC). Comprehensive examination of tumor biopsies and blood samples from these patients revealed that eosinophils, a type of immune cell typically involved in allergic reactions, were strongly increased in the blood and tumors of TNBC patients responding to immunotherapy. Using mouse models, we demonstrate that eosinophils are an essential link between other immune cells to induce immunotherapy responses. In the GELATO-trial, we investigated the clinical efficacy of twelve weeks of low-dose carboplatin in combination with immunotherapy in patients with metastatic lobular breast cancer and found this regimen to be mainly effective in patients with triple-negative lobular breast cancer. Furthermore, we demonstrate that breast tumors with low or moderate expression of the hormone receptor have comparable immunological characteristics as TNBC, thereby potentially identifying a subgroup that might benefit from immunotherapy. In summary, in this thesis we have identified new avenues that can be used to further investigate rationale immunotherapy combinations in breast cancer and to explore potential biomarkers for immunotherapy response.