“Immuno-radiotherapy” has recently appeared as a highly promising way to enhance immunotherapy
efficacy, based on the fact that radiation therapy (RT) locally induces immunogenic cell death and
therefore, could lead to a tumour-directed immune stimulation. For now, and despite preclinical
evidences of a synergistic action, few of these immuno-radiotherapy approaches have succeeded to
provide significant proof of benefits in the clinical setting, possibly because of the known deleterious
effects of RT on lymphocytes. Indeed, we presume that to be efficient, the ‘radiotherapy’ part of
immuno-radiotherapy regimens needs to be designed as the best immune-sparing treatment plan to allow
further tumour-directed immunostimulation, e.g., using immune-checkpoint blockers.
Therefore, the next-generation immuno-radiotherapy schemes will have to integrate novel constraints
that preserve lymphocyte-rich tissues to reduce the risk of RT-induced lymphopenia and
immunosenescence. More broadly, a drastic effort is needed to upgrade image-based tumour delineation
for RT planning, as of today, the routinely-used principles of GTV, CTV and PTV consider uncertainties
in planning and treatment delivery, incorporating margins for sub-clinical disease spread that cannot be
fully imaged. This implies negative effects on surrounding healthy tissues – including circulating blood
– without any clear benefit on tumour control, while it clearly impacts negatively immune cells.
We plan to introduce a game-changing immuno-radiotherapy paradigm by integrating into the routine
four main exploration axes: i/ leveraging the latest advances in digital pathology for precise image-based
tumour volume delineation, ii/ defining an immune organ at risk to be integrated in dose prescriptions,
iii/ deploying an integrated artificial intelligence (AI)-based treatment planning system that
automatically integrated immune constraints and iv/ exploring the potential of pharmacological immune
support based on an IL-15 superagonist immunomodulation. The proof of concept will be made in head
and neck squamous cell carcinoma, although our vision is to deliver novel clinically validated tools with
scalable application in multiple cancer types and stages.
In parallel, we will leverage immuno-RT possibilities to the next level to render it a reliable and easy-
to-implement option for oligometastatic cases who could be candidates to non-invasive ablative
treatment, e.g. in intent to cure. In the first place, this approach implies to improve patient selection and
even more precisely, intra-patient lesion selection among target lesions that could either respond or not
to immunotherapy, using radiomics-based prediction. Then, our plan is to move further the ‘one patient
one dose’ dogma, and build a lymphocyte-sparing multi-target holistic treatment selection pathway,
enabling ultra-personalised treatment of solid cancers.