Evidence for Early Stage Anti-Tumor Immunity Elicited by Spatially Fractionated Radiotherapy-Immunotherapy Combinations

Abstract

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An International Consensus on the Design of Prospective Clinical–Translational Trials in Spatially Fractionated Radiation Therapy

“…The inclusion of well-conducted translational science into clinical trial design is critically important to investigate in clinical patients the preclinically observed biological mechanisms and potential immunological phenomena of SFRT [15][16][17][18][19][20] . To accomplish this, "liquid biopsy" concepts, leveraged through serial blood and urine collections, synchronized prospectively with the treatment course, may advance our understanding of the underpinnings of SFRT response.…”

“…The inclusion of well-conducted translational science into clinical trial design is critically important to investigate in clinical patients the preclinically observed biological mechanisms and potential immunologic phenomena of SFRT. 15 , 16 , 17 , 18 , 19 , 20 To accomplish this, “liquid biopsy” concepts, leveraged through serial blood and urine collections and synchronized prospectively with the treatment course, may advance our understanding of the underpinnings of SFRT response. The challenge of the inability to procure tumor tissue during the radiation therapy course to interrogate molecular markers may be alleviated by prospective functional and molecular imaging.…”

“… 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 The observed enhanced tumoricidal effects of SFRT are thought to be related to the vastly inhomogeneous dose distributions. 4 , 14 , 15 The inherent advantages of ablative stereotactic radiosurgery or stereotactic radiation therapy like dose “peaks,” dispersed throughout the tumor, combined with interlaced low dose in the “valleys,” suited to preserve the tumor microenvironment and vasculature, are postulated to promote bystander and abscopal effects as potential underlying mechanisms for higher tumor response. 15 , 16 , 17 , 18 , 19 , 20 Such mechanisms are of particular interest in the current era of immune-modulating agents that are increasingly combined with radiation therapy.…”

Immune-Mediated Effects of Microplanar Radiotherapy with a Small Animal Irradiator

“…The key feature of spatially fractionated irradiation modalities, including MRT, in radiation-induced antitumor immunity is the unique distribution of high-dose and low-dose regions, simultaneously. Johnsrud et al have reported the synergic effect of GRID with immune checkpoint blockades [ 52 ]. The ablative effect of synchrotron-generated MRT on B16-F10 has been reported before, though it embedded FLASH effects [ 53 ].…”

Divide and conquer: spatially fractionated radiation therapy

“…Those presented markedly enhanced infiltration of both antigenpresenting cells and activated T cells, which were preceded by increased systemic IFN-γ production and led to eventual tumour growth delay (Ref. 125). T lymphocytes have also been shown to play a central role in the anti-tumour response in pMBRT (Ref.…”