Effets non ciblés (bystander, abscopal) de la radiothérapie externe : potentielles implications pour le clinicien ?

Sun, Roger; Sbai, Ali; Ganem, G.; Boudabous, M.; Collin, Fabrice; Marcy, Pierre-Yves; Doglio, Alain; Thariat, Juliette

doi:10.1016/j.canrad.2014.08.004

Cited by 13 publications

(8 citation statements)

References 63 publications

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“…However, the patient’s individual immune competence and immune escape mechanisms often hamper radio(chemo)therapy (RT)-induced abscopal effects ( 25 ). These findings further accentuate the necessity of a pretreatment patient stratification ( 26 , 27 ), and a continuous monitoring of immune responses during therapy ( 28 ). Presently, circulating proteins, exosomes, microRNAs and immune cell subpopulations are discussed as potential prognostic and predictive markers ( 29 – 33 ).…”

Section: Introductionmentioning

confidence: 87%

Dynamics of Heat Shock Protein 70 Serum Levels As a Predictor of Clinical Response in Non-Small-Cell Lung Cancer and Correlation with the Hypoxia-Related Marker Osteopontin

et al. 2017

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Hypoxia mediates resistance to radio(chemo)therapy (RT) by stimulating the synthesis of hypoxia-related genes, such as osteopontin (OPN) and stress proteins, including the major stress-inducible heat shock protein 70 (Hsp70). Apart from its intracellular localization, Hsp70 is also present on the plasma membrane of viable tumor cells that actively release it in lipid vesicles with biophysical characteristics of exosomes. Exosomal Hsp70 contributes to radioresistance while Hsp70 derived from dying tumor cells can serve as a stimulator of immune cells. Given these opposing traits of extracellular Hsp70 and the unsatisfactory outcome of locally advanced lung tumors, we investigated the role of Hsp70 in the plasma of patients with advanced, non-metastasized non-small-cell lung cancer (NSCLC) before (T1) and 4–6 weeks after RT (T2) in relation to OPN as potential biomarkers for clinical response. Plasma levels of Hsp70 correlate with those of OPN at T1, and high OPN levels are significantly associated with a decreased overall survival (OS). Due to a therapy-induced reduction in viable tumor mass after RT Hsp70 plasma levels dropped significantly at T2 (p = 0.016). However, with respect to the immunostimulatory capacity of Hsp70 derived from dying tumor cells, patients with higher post-therapeutic Hsp70 levels showed a significantly better response to RT (p = 0.034) than those with lower levels at T2. In summary, high OPN plasma levels at T1 are indicative for poor OS, whereas elevated post-therapeutic Hsp70 plasma levels together with a drop of Hsp70 between T1 and T2, successfully predict favorable responses to RT. Monitoring the dynamics of Hsp70 in NSCLC patients before and after RT can provide additional predictive information for clinical outcome and therefore might allow a more rapid therapy adaptation.

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Section: Introductionmentioning

confidence: 87%

Dynamics of Heat Shock Protein 70 Serum Levels As a Predictor of Clinical Response in Non-Small-Cell Lung Cancer and Correlation with the Hypoxia-Related Marker Osteopontin

et al. 2017

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“…Un exemple d'une telle immunomodulation est représenté par les « effet de voisinage » de l'irradiation, ce qui signifie que l'irradiation peut avoir un effet sur croissance de tumeurs situées en dehors des zone irradiées. Le terme abscopal (en dehors du champ) a été défini pour décrire les effets éloignés du site initial de l'irradiation [24,25]. Les mécanismes immunitaires innés pourraient avoir un rôle dans les effets systémiques après irradiation localisée.…”

Section: Modulation Du Système Immunitaireunclassified

Radiothérapie et immunomodulation : mise au point sur les données expérimentales

Deutsch

Lévy

Chargari

2015

Cancer/Radiothérapie

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“…Although less well investigated, a third type of non-targeted effect—the cohort effect—is defined as the interaction between irradiated cells within an irradiated volume where, under heterogeneous irradiation, high-dose-irradiated cells might affect low-dose-irradiated cells, and vice versa; 13 the cohort effect is limited to an area of millimetres within the target. 14 …”

Section: Introductionmentioning

confidence: 99%

“…However, as the scope of this review is beyond describing the features of each effect in detail or detailing the interplay between radiation and immunity, we invite readers to refer to other comprehensive reviews on this topic (for reviews see refs. 12 , 14 – 20 ). Briefly, though, the main mechanism responsible for the bystander effect involves direct gap-junction-mediated cell–cell communication via ions such as calcium and small molecules such as nitric oxide, although other factors such as transforming growth factor-β (TGF-β), cytokines and chemokines can also be released in the extracellular compartment, triggering local immune activation (Fig.…”

Section: Introductionmentioning

confidence: 99%

Radiation-induced bystander and abscopal effects: important lessons from preclinical models

Daguenet¹,

Louati²,

Wozny³

et al. 2020

Br J Cancer

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Radiotherapy is a pivotal component in the curative treatment of patients with localised cancer and isolated metastasis, as well as being used as a palliative strategy for patients with disseminated disease. The clinical efficacy of radiotherapy has traditionally been attributed to the local effects of ionising radiation, which induces cell death by directly and indirectly inducing DNA damage, but substantial work has uncovered an unexpected and dual relationship between tumour irradiation and the host immune system. In clinical practice, it is, therefore, tempting to tailor immunotherapies with radiotherapy in order to synergise innate and adaptive immunity against cancer cells, as well as to bypass immune tolerance and exhaustion, with the aim of facilitating tumour regression. However, our understanding of how radiation impacts on immune system activation is still in its early stages, and concerns and challenges regarding therapeutic applications still need to be overcome. With the increasing use of immunotherapy and its common combination with ionising radiation, this review briefly delineates current knowledge about the non-targeted effects of radiotherapy, and aims to provide insights, at the preclinical level, into the mechanisms that are involved with the potential to yield clinically relevant combinatorial approaches of radiotherapy and immunotherapy.

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Effets non ciblés (bystander, abscopal) de la radiothérapie externe : potentielles implications pour le clinicien ?

Cited by 13 publications

References 63 publications

Dynamics of Heat Shock Protein 70 Serum Levels As a Predictor of Clinical Response in Non-Small-Cell Lung Cancer and Correlation with the Hypoxia-Related Marker Osteopontin

Dynamics of Heat Shock Protein 70 Serum Levels As a Predictor of Clinical Response in Non-Small-Cell Lung Cancer and Correlation with the Hypoxia-Related Marker Osteopontin

Radiothérapie et immunomodulation : mise au point sur les données expérimentales

Radiation-induced bystander and abscopal effects: important lessons from preclinical models

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