Special Issue "Advances in Radiation Immuno-Oncology: Progress at the Interface of Radiation Oncology and Immunotherapy—A Themed Issue in Honor of Prof. Dr. Gabriele Multhoff"

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 31 January 2024 | Viewed by 3909

Special Issue Editors

1. The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK
2. CEO of Multimmune GmbH, Munich, Germany
Interests: cancer immunotherapy; heat shock proteins; immunoregulation; cancer therapeutics; cancer diagnostics; tumor immunity
Head of Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Erlangen, Germany
Interests: immune modulation by radiation; tumor immunology; hyperthermia; vaccination; osteoimmunological mechanisms of low-dose radiation therapy; translational immune monitoring; combined radio- immunotherapies; prognostic and predictive immune biomarkers
Special Issues, Collections and Topics in MDPI journals
Department of Radiotherapy and Oncology, Goethe University Frankfurt am Main, 60590 Frankfurt am Main, Germany
Interests: translational research; biomarker development; cancer radioimmunotherapy; low-dose anti-inflammatory radiation therapy; tumor microenviroment; survivin; molecular targeting

Special Issue Information

Dear Colleagues, 

Prof. Dr. Gabriele Multhoff is Professor of Experimental Radiation Oncology and Radiation Biology and Head of the Radiation Immuno-Oncology Group at the Center for Translational Cancer Research (TranslaTUM) and the Department of Radiation Oncology at the Technical University of Munich (TUM), Klinikum rechts der Isar in Munich, Germany.

After studying biology at the Ludwig Maximilians Universität (LMU) Munich, Prof. Multhoff obtained her doctorate in immunology in 1990 and habilitated within the framework of a Möllemann habilitation scholarship in 1998. In 2002, she was appointed Professor of Experimental Hematology at the University Hospital Regensburg, from where she moved to her current position in 2007. Prof. Multhoff is also the founder, former CEO and current CSO of multimmune GmbH. In 2015, Prof. Dr. Gabriele Multhoff was awarded the 2015 CESAR (Central European Society of Anticancer Drug Research) Prize for outstanding work in the field of translational research on the development of anti-tumor agents, specifically her work on innovative cellular, molecular and antibody-mediated immunotherapies.

Prof. Gabriele Multhoff’s research focusses on the development of innovative cell-, molecule- and antibody-based targeted immunotherapies that are primarily based on her seminal discovery that tumors selectively express a membrane form of heat shock protein 70 (Hsp70), and she is combining these new therapeutic approaches with conventional radiation therapy and chemotherapy. Her work has led to the successful delivery of a randomized, multicenter phase II clinical study entitled “Targeted NK cell-based adjuvant immunotherapy for the treatment of patients with non-small cell lung carcinoma (NSCLC) after radiochemotherapy”. Her group has established a novel screening test to quantify liposomal, tumor-derived Hsp70 and a method to isolate circulating tumor cells (CTCs) from patients with a variety of cancers.

Prof. Multhoff’s research interests also include the application of novel in vivo imaging techniques such as intraoperative, fluorescence molecular tomography (FMT), multispectral optoacoustic tomography (MSOT) and PET/CT after CT-guided irradiation of tumors and the analysis of cellular, molecular biological and immunological mechanisms in tumors and normal cells, including primary endothelial cells, after exposure to radiation, as well as the development of innovative nanoparticle-based theranostica.

Based on her sustained, impressive contributions to the field and their translational relevance, we are delighted to act as Guest Editors for this Special Issue of Cancers honoring her significant achievements. The prime focus of this Special Issue is to highlight her outstanding achievements in translational radiation immuno-oncology and her critical role in advancing the field. We are very pleased to invite Gabriele Multhoff’s collaborators and peers to submit a publication to this Special Issue, which we believe will stimulate thought and make a unique contribution to the field.

Prof. Dr. A. Graham Pockley
Prof. Dr. Udo S. Gaipl
Prof. Dr. Franz Rödel
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


  • radiation oncology
  • radiotherapy
  • tumor immunity
  • immuno-oncology
  • cancer immunotherapy
  • cancer therapeutics
  • cancer diagnostics
  • cancer theranostics
  • imaging

Published Papers (2 papers)

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Elevated Levels of Circulating Hsp70 and an Increased Prevalence of CD94+/CD69+ NK Cells Is Predictive for Advanced Stage Non-Small Cell Lung Cancer
Cancers 2022, 14(22), 5701; https://doi.org/10.3390/cancers14225701 - 21 Nov 2022
Cited by 3 | Viewed by 1448
Non-small cell lung cancer (NSCLC) is the second most frequently diagnosed tumor worldwide. Despite the clinical progress which has been achieved by multimodal therapies, including radiochemotherapy, and immune checkpoint inhibitor blockade, the overall survival of patients with advanced-stage NSCLC remains poor, with less [...] Read more.
Non-small cell lung cancer (NSCLC) is the second most frequently diagnosed tumor worldwide. Despite the clinical progress which has been achieved by multimodal therapies, including radiochemotherapy, and immune checkpoint inhibitor blockade, the overall survival of patients with advanced-stage NSCLC remains poor, with less than 16 months. It is well established that many aggressive tumor entities, including NSCLC, overexpress the major stress-inducible heat shock protein 70 (Hsp70) in the cytosol, present it on the plasma membrane in a tumor-specific manner, and release Hsp70 into circulation. Although high Hsp70 levels are associated with tumor aggressiveness and therapy resistance, membrane-bound Hsp70 can serve as a tumor-specific antigen for Hsp70-primed natural killer (NK) cells, expressing the C-type lectin receptor CD94, which is part of the activator receptor complex CD94/NKG2C. Therefore, we investigated circulating Hsp70 levels and changes in the composition of peripheral blood lymphocyte subsets as potential biomarkers for the advanced Union for International Cancer Control (UICC) stages in NSCLC. As expected, circulating Hsp70 levels were significantly higher in NSCLC patients compared to the healthy controls, as well as in patients with advanced UICC stages compared to those in UICC stage I. Smoking status did not influence the circulating Hsp70 levels significantly. Concomitantly, the proportions of CD4+ T helper cells were lower compared to the healthy controls and stage I tumor patients, whereas that of CD8+ cytotoxic T cells was progressively higher. The prevalence of CD3−/CD56+, CD3−/NKp30, CD3−/NKp46+, and CD3−/NKG2D+ NK cells was higher in stage IV/IIIB of the disease than in stage IIIA but were not statistically different from that in healthy individuals. However, the proportion of NK cells expressing CD94 and the activation/exhaustion marker CD69 significantly increased in higher tumor stages compared with stage I and the healthy controls. We speculate that although elevated circulating Hsp70 levels might promote the prevalence of CD94+ NK cells in patients with advanced-stage NSCLC, the cytolytic activity of these NK cells also failed to control tumor growth due to insufficient support by pro-inflammatory cytokines from CD4+ T helper cells. This hypothesis is supported by a comparative multiplex cytokine analysis of the blood in lung cancer patients with a low proportion of CD4+ T cells, a high proportion of NK cells, and high Hsp70 levels versus patients with a high proportion of CD4+ T cells exhibiting lower IL-2, IL-4, IL-6, IFN-γ, granzyme B levels. Full article
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From Localized Mild Hyperthermia to Improved Tumor Oxygenation: Physiological Mechanisms Critically Involved in Oncologic Thermo-Radio-Immunotherapy
Cancers 2023, 15(5), 1394; https://doi.org/10.3390/cancers15051394 - 22 Feb 2023
Cited by 3 | Viewed by 1752
(1) Background: Mild hyperthermia (mHT, 39–42 °C) is a potent cancer treatment modality when delivered in conjunction with radiotherapy. mHT triggers a series of therapeutically relevant biological mechanisms, e.g., it can act as a radiosensitizer by improving tumor oxygenation, the latter generally believed [...] Read more.
(1) Background: Mild hyperthermia (mHT, 39–42 °C) is a potent cancer treatment modality when delivered in conjunction with radiotherapy. mHT triggers a series of therapeutically relevant biological mechanisms, e.g., it can act as a radiosensitizer by improving tumor oxygenation, the latter generally believed to be the commensurate result of increased blood flow, and it can positively modulate protective anticancer immune responses. However, the extent and kinetics of tumor blood flow (TBF) changes and tumor oxygenation are variable during and after the application of mHT. The interpretation of these spatiotemporal heterogeneities is currently not yet fully clarified. (2) Aim and methods: We have undertaken a systematic literature review and herein provide a comprehensive insight into the potential impact of mHT on the clinical benefits of therapeutic modalities such as radio- and immuno-therapy. (3) Results: mHT-induced increases in TBF are multifactorial and differ both spatially and with time. In the short term, changes are preferentially caused by vasodilation of co-opted vessels and of upstream normal tissue vessels as well as by improved hemorheology. Sustained TBF increases are thought to result from a drastic reduction of interstitial pressure, thus restoring adequate perfusion pressures and/or HIF-1α- and VEGF-mediated activation of angiogenesis. The enhanced oxygenation is not only the result of mHT-increased TBF and, thus, oxygen availability but also of heat-induced higher O2 diffusivities, acidosis- and heat-related enhanced O2 unloading from red blood cells. (4) Conclusions: Enhancement of tumor oxygenation achieved by mHT cannot be fully explained by TBF changes alone. Instead, a series of additional, complexly linked physiological mechanisms are crucial for enhancing tumor oxygenation, almost doubling the initial O2 tensions in tumors. Full article
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Reprogramming the immunosuppressive tumor microenvironment to improve responses to radiation therapy and immunotherapy combinations
Authors: Tim Illidge
Affiliation: Faculty of Biology, Medicine and Health, The University of Manchester, The Christie NHS Foundation Trust
Abstract: Radiotherapy (RT) is an important part of cancer treatment delivered to around 50% of all cancer patients. In addition to its direct tumoricidal effects RT can induce profound immunomodulatory effects in the surrounding tumor microenvironment (TME) which can be both immunostimulatory and immunosuppressive. Immune checkpoint inhibitors (ICIs) directed against the programmed death ligand 1 (PD-L1) and Cytotoxic T-Lymphocyte associated antigen 4 (CTLA-4) have revolutionized cancer therapy but are only effective in a minority of patients. Hundreds of clinical trials have been set-up investigating whether response rates and clinical outcomes could be improved with the combination of RT and ICIs. Reported results thus far have been disappointing and further investigation is required to understand the underlying mechanisms of therapeutic resistance to ICI and RT induced immunosuppression. In this review the focus will be on mechanisms of RT induced immunosuppression including within the TME, including myeloid-derived suppressor cells (MDSC), regulatory T cells (Tregs) and macrophage populations and evolving therapeutic strategies to reprogramming the immunosuppressive TME. Emerging new approaches to overcome therapeutic resistance and improve responses to increase the generation of local and systemic anti-cancer immune response following RT and immunomodulatory agents, are discussed.

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