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Cancers
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The Effect of Radiation Therapy on the Tumor Ecosystem
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The Effect of Radiation Therapy on the Tumor Ecosystem

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

Deadline for manuscript submissions: closed (1 May 2024) | Viewed by 6131

Special Issue Editor

Dr. Vincent Potiron

E-Mail Website
Guest Editor
1. Institut de Cancérologie de l’Ouest, Département de Radiothérapie, 44800 Saint Herblain, France
2. CNRS UMR 6286, Université de Nantes, 44322 Nantes, France
Interests: tumor vascular microenvironment; radiobiology; FLASH radiotherapy

Special Issue Information

Dear Colleagues,

Radiotherapy is used in more than 50% of cancer patients with curative and/or palliative intent, making it one of the most common and powerful treatments. Whereas the killing of clonogenic tumor cells remains the primary goal, the biological response of the tumor microenvironment has been proved to regulate local tumor control, metastatic disease spreading as well as the occurrence of side effects. Vascular remodeling, immune modulation and fibrosis represent only some of the responses governed by non-tumor cells upon radiation treatment, and interact mutually in what can be considered globally as a tumor ecosystem. Identifying the cardinal landmarks of this system represents a field of opportunities to improve treatment, medical imaging, diagnostics and prognostics.

This Special Issue aims to place emphasis on the tumor microenvironment in the context of ionizing radiation therapies. Research areas may include fundamental mechanisms and signaling, translational or preclinical studies, bioengineering and technical breakthroughs. We welcome research articles, reviews offering comprehensive data or innovative opinions, (positive) clinical studies with direct targeting of the microenvironment, as well as in silico works, provided they highlight the contribution of non-tumor cells.

We look forward to receiving your contributions promoting this exciting scientific field.

Dr. Vincent Potiron
Guest Editor

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 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.

Keywords

  • radiotherapy
  • ionizing radiation
  • tumor microenvironment
  • tumor angiogenesis
  • anti-tumor immunity
  • fibrosis

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Published Papers (2 papers)

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Research

21 pages, 3712 KiB  
Article
Macrophage Resistance to Ionizing Radiation Exposure Is Accompanied by Decreased Cathepsin D and Increased Transferrin Receptor 1 Expression
by Ana Teresa Pinto, Ana Beatriz Machado, Hugo Osório, Marta Laranjeiro Pinto, Rui Vitorino, Gonçalo Justino, Cátia Santa, Flávia Castro, Tânia Cruz, Carla Rodrigues, Jorge Lima, José Luís R. Sousa, Ana Patrícia Cardoso, Rita Figueira, Armanda Monteiro, Margarida Marques, Bruno Manadas, Jarne Pauwels, Kris Gevaert, Marc Mareel, Sónia Rocha, Tiago Duarte and Maria José Oliveiraadd Show full author list remove Hide full author list
Cancers 2023, 15(1), 270; https://doi.org/10.3390/cancers15010270 - 30 Dec 2022
Cited by 2 | Viewed by 3225
Abstract
Purpose: To identify a molecular signature of macrophages exposed to clinically relevant ionizing radiation (IR) doses, mirroring radiotherapy sessions. Methods: Human monocyte-derived macrophages were exposed to 2 Gy/ fraction/ day for 5 days, mimicking one week of cancer patient’s radiotherapy. Protein expression profile [...] Read more.
Purpose: To identify a molecular signature of macrophages exposed to clinically relevant ionizing radiation (IR) doses, mirroring radiotherapy sessions. Methods: Human monocyte-derived macrophages were exposed to 2 Gy/ fraction/ day for 5 days, mimicking one week of cancer patient’s radiotherapy. Protein expression profile by proteomics was performed. Results: A gene ontology analysis revealed that radiation-induced protein changes are associated with metabolic alterations, which were further supported by a reduction of both cellular ATP levels and glucose uptake. Most of the radiation-induced deregulated targets exhibited a decreased expression, as was the case of cathepsin D, a lysosomal protease associated with cell death, which was validated by Western blot. We also found that irradiated macrophages exhibited an increased expression of the transferrin receptor 1 (TfR1), which is responsible for the uptake of transferrin-bound iron. TfR1 upregulation was also found in tumor-associated mouse macrophages upon tumor irradiation. In vitro irradiated macrophages also presented a trend for increased divalent metal transporter 1 (DMT1), which transports iron from the endosome to the cytosol, and a significant increase in iron release. Conclusions: Irradiated macrophages present lower ATP levels and glucose uptake, and exhibit decreased cathepsin D expression, while increasing TfR1 expression and altering iron metabolism. Full article
(This article belongs to the Special Issue The Effect of Radiation Therapy on the Tumor Ecosystem)
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16 pages, 1962 KiB  
Article
Quantifying the Effects of Combination Trastuzumab and Radiation Therapy in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer
by Meghan J. Bloom, Patrick N. Song, John Virostko, Thomas E. Yankeelov and Anna G. Sorace
Cancers 2022, 14(17), 4234; https://doi.org/10.3390/cancers14174234 - 31 Aug 2022
Cited by 4 | Viewed by 2275
Abstract
Background: Trastuzumab induces cell cycle arrest in HER2-overexpressing cells and demonstrates potential in radiosensitizing cancer cells. The purpose of this study is to quantify combination trastuzumab and radiotherapy to determine their synergy. Methods: In vitro, HER2+ cancer cells were treated with trastuzumab, radiation, [...] Read more.
Background: Trastuzumab induces cell cycle arrest in HER2-overexpressing cells and demonstrates potential in radiosensitizing cancer cells. The purpose of this study is to quantify combination trastuzumab and radiotherapy to determine their synergy. Methods: In vitro, HER2+ cancer cells were treated with trastuzumab, radiation, or their combination, and imaged to evaluate treatment kinetics. In vivo, HER2+ tumor-bearing mice were treated with trastuzumab and radiation, and assessed longitudinally. An additional cohort was treated and sacrificed to quantify CD45, CD31, α-SMA, and hypoxia. Results: The interaction index revealed the additive effects of trastuzumab and radiation in vitro in HER2+ cell lines. Furthermore, the results revealed significant differences in tumor response when treated with radiation (p < 0.001); however, no difference was seen in the combination groups when trastuzumab was added to radiotherapy (p = 0.56). Histology revealed increases in CD45 staining in tumors receiving trastuzumab (p < 0.05), indicating potential increases in immune infiltration. Conclusions: The in vitro results showed the additive effect of combination trastuzumab and radiotherapy. The in vivo results showed the potential to achieve similar efficacy of radiotherapy with a reduced dose when combined with trastuzumab. If trastuzumab and low-dose radiotherapy induce greater tumor kill than a higher dose of radiotherapy, combination therapy can achieve a similar reduction in tumor burden. Full article
(This article belongs to the Special Issue The Effect of Radiation Therapy on the Tumor Ecosystem)
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