Lecture Dr. Carine Michiels | Immunogenic cell death and radiotherapy: how to make them working together

Immunogenic cell death and radiotherapy: how to make them working together 

In response to radiotherapy, rare clinical cases have shown an abscopal effect, defined as the regression of tumors/metastases outside the irradiated field. The hypothesis is that this effect occurs through the induction of an antitumor immune response. The objective of our work is to determine whether protons would be able to induce greater antitumor immunity than that induced by X-rays in two syngeneic mouse cancer models. In vitro results showed the activation of the cGAS-STING pathway and type I IFN response after X-ray and proton irradiation. In addition, the expression of several immunosuppressive factors such as PD-L1, IL-10, IDO-1, and CD80/CD86 was increased after both types of irradiation. The mechanisms underlying PD-L1 overexpression were investigated since it may provide a way to stratify patients for immune checkpoint blocker therapy.

In addition, an in vivo vaccination trial demonstrated, in one of the two models (C3H/HeN syngeneic mouse model) but not in the other, an anti-tumor response induced by cancer cells irradiated with X-rays but not with protons. Depletion of CD8+ T cells abolished the antitumor response, highlighting the need for functional CD8+ T cells to trigger the systemic antitumor response induced by irradiation. These data highlight the potential benefits of using radiotherapy in combination with immunotherapy in the clinic to improve patient response to treatment.