Radiotherapy–immunotherapy combinations – perspectives and challenges

Michele Mondini (1) , Antonin Levy (1, 2) , Lydia Meziani (1) , Fabien Milliat (3) , Eric Deutsch (1, 2)

1 RaMo-IT - Radiothérapie Moléculaire et Innovation Thérapeutique
2 Département de radiothérapie [Gustave Roussy]
3 IRSN/PSE-SANTE/SERAMED/LRMed - Laboratoire de Radiobiologie des expositions médicales

Ionizing radiation was historically used to treat cancer to kill tumour cells, in particular by inducing DNA damage. This view of radiotherapy (RT) as a simple cytotoxic agent has dramatically changed in the last years, and it is now widely accepted that RT can deeply reshape the tumour environment, in particular by modulating the immune response. Such evidence gives a strong rationale to use immunomodulators to boost the therapeutic value of RT, opening the era of “immunoradiotherapy”. The increasing amount of preclinical and clinical data concerning the combination of immunomodulators with RT, and in particular with immune checkpoints inhibitors as anti-PD1/PDL1 and anti-CTLA4, reflects the interest of the scientific and medical community concerning immunoradiotherapy. The expectations are enormous, since the rational for performing such combinations is strong, and the possibility to use a local treatment as RT to amplify a systemic antitumor response, as in the cases of the abscopal effect. Nevertheless, several points remain to be addresses as the need to find biomarkers to selected patients that will benefit from immunoradiotherapy, the identification of the best sequences/schedules for combination with immunomodulators, how to overcome resistance. Also, the effects of immunoradiotherapy on healthy tissues and related toxicity remains largely unexplored. To answers these critical questions and make immunoradiotherapy keep its promises, large efforts are needed from both the pharmaceutical industry and the academic/governmental research. Moreover, thanks to the work of both these players, the arsenal of available immunomodulators is quickly expanding, thus opening the field to more and more combinations with RT. We thus forecast that the field of immunoradiotherapy will further expand in the next years, and it needs to be supported by appropriate investment plans.

Mots clés: abscopal effect; immune modulation; immunotherapy; radiotherapy; toxicity; abscopaleffect

Domaines: Sciences du Vivant [q-bio]

Michele Mondini, Antonin Levy, Lydia Meziani, Fabien Milliat, Eric Deutsch. Radiotherapy–immunotherapy combinations – perspectives and challenges. Molecular Oncology, 2020, 14 (7), pp.1529-1537. ⟨10.1002/1878-0261.12658⟩. ⟨hal-03156487v2⟩