Current Methods for Enhancing Radioimmunotherapies: Combining Radiotherapy with Immunomodulatory Treatment

TOPICAL COLLECTIONS

Guest Editors

Michael Rückert

Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg

Dr. Michael Rückert is a researcher in the Translational Radiobiology group of Prof. Gaipl at the Department of Radiation Oncology, Universitätsklinikum Erlangen. During his doctoral studies, he researched the induction of systemic anti-tumor immune responses through a combination of local hypofractionated radiotherapy, immune checkpoint inhibition, and an experimental tumor cell vaccine generated by inactivating tumor cells with high hydrostatic pressure. After receiving his Dr. rer. nat. in 2020, he now leads the group 'Systemic Anti-Tumor Immune Responses'. His group is particularly interested in investigating how radiotherapy and other treatments modulate the immune phenotype of tumor cells. In particular, they are investigating the impact of poorly understood immune checkpoint molecules on the immune suppression of tumors.

Lisa Deloch

Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg

Dr. Lisa Deloch is group leader of the Radiation-Osteoimmunology Group in the Translational Radiobiology group of Prof. Gaipl at the Department of Radiation Oncology, Universitätsklinikum Erlangen. There she is looking into the anti-inflammatory, immunomodulating, and osteoimmunological effects that are mediated by low-dose radiotherapy (LD-RT) with X-rays. Special focus within this work is set on bone cells as well as macrophages, T cells and fibroblast-like synoviocytes. Furthermore, her group is also investigating the age-/gender- and inflammatory background mediated differences in response to ionizing radiation in a medical and radiation protection setting. Here, next to X-rays, her group is also examining the effects of radon, mixed beam irradiation, and protons on the immune system.

Collection Overview

The immunomodulatory effects of radiotherapy (RTx) have received little attention and research. In the meantime, it is known that complex factors influence both the tumor and the tumor microenvironment. Although immune checkpoint inhibitors have shown great success in recent years, most patients do not respond to this treatment. Experiments in preclinical models highlight the synergy of combining RTx and immunotherapy to improve local tumor control and induce systemic anti-tumor immune responses.

However, translating these preclinical findings into successful clinical trials has been challenging, as both treatments must closely match each other and the patient. Thus, it is essential to understand how RTx modulates immune responses in both the tumor and immune cells and how these effects can be leveraged in multimodal treatment.

This Methods Collection aims to explore preclinical and clinical research methods for developing future radioimmunotherapy approaches. Topics of interest include, but are not limited to:

Improving the immunogenicity of RTx (e.g., dose, fractionation, timing)

Combining treatment modalities to enhance systemic anti-tumor immune responses

Animal models of radioimmunotherapies

Improving current in vivo and ex vivo protocols (e.g., modulation of the tumor immune phenotype, tumor and immune cell interactions)

Metabolomic studies of immune cells after RTx

Immune monitoring of patients after RTx and immunotherapy (e.g., prognostic markers, biomarkers, patient stratification)

Other immune modulatory treatment options complementary to RTx (e.g., hyperthermia)