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Despite the recent progress, current treatment modalities are not able to eradicate cancer. We show that Microbeam Radiotherapy (MRT), an innovative type of Spatially Fractionated Radiotherapy, can control murine melanoma by activating the host's own immune system. The beneficial effects are very pronounced in comparison to uniform radiotherapy traditionally employed in the clinic. Our results show that MRT increased antigen presentation, activating Cytotoxic T Lymphocytes (CTLs) which are essential to MRT's treatment efficacy in melanoma. Depletion of CTLs abrogated treatment response. Multiplex nucleic acid hybridization technology revealed key features of lymphocyte populations such as proliferation, differentiation, and ligand-receptor interactions. In addition, CTLs were shown to be essential for locoregional metastatic control and systemic abscopal effects confirmed by activation of antigen presenting cells and CTL trafficking in the tumour-draining lymph nodes. MRT also showed a synergistic effect with immunotherapy. Overall, MRT induces a robust antitumour immune response, acting like an in situ vaccination, which could be exploited to treat a variety of treatment-resistant malignancies. • Broad study of immune responses induced by microbeam radiotherapy (MRT) in melanoma. • MRT increases antigen presentation and Cytotoxic T Lymphocyte (CTL) infiltration. • CTLs are essential for tumour control and metastatic delay in lymph nodes after MRT. • MRT shows a synergistic effect with immunotherapy. • MRT elicits an in situ vaccination effect in melanoma.
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Trappetti et al. (2024) studied this question.
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