Radiobiology of Tumours
W. P. M. Mayles, A. E. Nahum, J.-C. Rosenwald in Handbook of Radiotherapy Physics, 2021
It is, however, unlikely to be always necessary to eradicate the last clonogenic tumour cell to achieve local tumour control.* Radiation can activate immune responses by enhancing antigen presentation and tumour immunogenicity, and increasing the production of cytokines (Bernstein et al. 2016). Localised radiation to tumours can lead to systemic responses at distant sites, a phenomenon known as the abscopal effect (Golden et al. 2015). There is a need to understand how radiation dose and schedule affects immune response mechanisms in preclinical studies and apply new knowledge in the clinic to improve patient outcomes. In 2011, it was stated that ‘cancer immunotherapy comes of age' (Mellman et al. 2011), and combining it with radiotherapy is a current ‘hot' topic in radiation research.
Multi-scale modeling approaches: application in chemo– and immuno–therapies
Issam El Naqa in A Guide to Outcome Modeling in Radiotherapy and Oncology, 2018
Modulating the interplay between the immune system and cancer cells via immunotherapy alone or on in combination with other therapeutics is becoming one of the most promising cancer treatment approaches. Due to the complexity of this interplay, computational modeling methods are playing a pivotal role [463]. A summary of such efforts using different modeling approaches is shown in Figure 11.9 [485]. For instance, an agent-based (cf. Section 11.3.2) model was used to study the effects of a specific immunotherapy strategy against B16-melanoma cell lines in mice and to predict the role of CD137 (tumor necrosis factor (TNF) receptor family) expression on tumor vessel endothelium for successful therapy [486]. Another study applied a discrete-time pharmacodynamic model to illustrate the potential synergism between immune checkpoint inhibitors (PD1-PDL1 axis and/or the CTLA-4) and radiotherapy. The effects of irradiation were described by a modified version of the linear-quadratic (LQ) model [487]. The model was able to explain the biphasic relationship between the size of a tumor and its immunogenicity, as measured by the abscopal effect, i.e., an induced non-localized immune response. Moreover, it explained why discontinuing immunotherapy may result in either tumor recurrence or a durably sustained response indicating potential for better synergistic scheduling [487].
Radiation Dermatitis
Gabriella Fabbrocini, Mario E. Lacouture, Antonella Tosti in Dermatologic Reactions to Cancer Therapies, 2019
Possession of an unpaired electron causes molecules to undergo deleterious transmutations in an effort to establish stability. In the case of DNA, these transmutations can lead to strand breakage, nucleotide loss, nucleotide dimerization, and more (3). Mitotic catastrophe, apoptosis, necrosis, and senescence are all common modes of cell death following radiation (6). In some cases, radiation-induced cell death leads to an antitumor immune response. This phenomenon, called the abscopal effect, results in regression of untreated metastases and may be enhanced by immunomodulating cancer therapies (e.g., ipilimumab) (7).
Radiation-induced augmentation in dendritic cell function is mediated by apoptotic bodies/STAT5/Zbtb46 signaling
Published in International Journal of Radiation Biology, 2020
Vipul K. Pandey, Bhavani S. Shankar
The activation of immune system has also been used to explain the abscopal effect in radiotherapy. Abscopal effect is the phenomenon due to which localized radiotherapy of a tumor causes not only decrease of the treated tumor, but also reduction of tumors outside the scope of the treatment. This is particularly important in the treatment of metastatic cancers. Such a reduction of tumor mass at a distant site in a metastatic melanoma patient was preceded by activation of myeloid-lineage cells, including increased HLA-DR expression on DC, supporting the idea that systemic increase in immune system after radiotherapy can be the reason for abscopal effects (Postow et al. 2012). Similarly, secondary tumor reduction was observed when mice bearing mammary carcinoma 67NR were treated with 2 Gy of primary tumor-specific radiation and Flt3 ligand, suggesting role of DC in abscopal effects (Demaria et al. 2004).
Challenges in the combination of radiotherapy and immunotherapy for breast cancer
Published in Expert Review of Anticancer Therapy, 2023
Rui Zhang, Samantha D Clark, Beibei Guo, Tianyi Zhang, Duane Jeansonne, Samithamby J Jeyaseelan, Joseph Francis, Weishan Huang
The abscopal effect, which describes the anticancer effect on tumor cells located distant from the locally treated site, was originally described by Mole in 1953 for radiation [38], but this concept has been expanded nowadays because literature shows other local therapies can also cause abscopal effect [39–41]. The abscopal effect has been reported for various cancers including breast cancer over the years [42]. Considering that the majority of deaths due to breast cancer are a consequence of metastatic disease [1,43], the abscopal effect may effectively suppress or eliminate the distant cancer cells and significantly benefit breast cancer patients. However, the abscopal effect arising from RT alone is exceedingly rare, and only 46 cases were reported between 1969 and 2014 [44]. Pre-clinical studies show the abscopal effect is mediated by the immune system [45,46]. Although RT can promote proliferation and priming of T cells, the concentration of fully functional T cells induced by radiation alone is usually not sufficient to elicit an antitumor immunity due to the immunosuppressive tumor microenvironment associated with established tumors, which partially explains the rarity of abscopal effects caused by RT alone.
Overview of the synergistic use of radiotherapy and immunotherapy in cancer treatment: current challenges and scopes of improvement
Published in Expert Review of Anticancer Therapy, 2023
Riccardo Ray Colciago, Irene Fischetti, Carlotta Giandini, Eliana La Rocca, Tiziana Rancati T., Alicia Rejas Mateo, Mario Paolo Colombo, Laura Lozza, Claudia Chiodoni, Elena Jachetti, Maria Carmen De Santis
Abscopal is a word created by joining the prefix ab-, meaning ‘position away from’ and scopus (Latin), meaning ‘mark or target for shooting at’ [20]. Therefore, in oncology, ‘ab-scopal’ means ‘at a distance from the irradiated volume but within the same organism.’ In other words, abscopal effect reflects the complete response of unirradiated metastatic lesions at a distance from the primary irradiation site, mediated by a systemic anti-tumor immune response [20]. The National Cancer Institute defines abscopal effect as: ‘The shrinking or disappearance of tumours in parts of the body that were not the direct targets of local therapy, such as radiation therapy. It is considered that in abscopal effect, the immune system is stimulated to fight cancer in the whole body as a result of local therapy’ [21].
Related Knowledge Centers
- Ionizing Radiation
- Ipilimumab
- Metastasis
- Pembrolizumab
- Dendritic Cell
- Antigen
- Radiation Therapy
- Targeted Intra-Operative Radiotherapy
- Priming
- Antigen-Presenting Cell