Shifting the immune-suppressive to predominant immune-stimulatory radiation effects by sbrt-partial tumor irradiation targeting hypoxic segment (Sbrt-pathy)

Slavisa Tubin, Seema Gupta, Michael Grusch, Helmuth H. Popper, Luka Brcic, Martin L. Ashdown, Samir N. Khleif, Barbara Peter-Vörösmarty, Martin Hyden, Simone Negrini, Piero Fossati, Eugen Hug

Research output: Contribution to journalReview articlepeer-review

Abstract

Radiation-induced immune-mediated abscopal effects (AE) of conventional radiotherapy are very rare. Whole-tumor irradiation leads to lymphopenia due to killing of immune cells in the tumor microenvironment, resulting in immunosuppression and weak abscopal potential. This limitation may be overcome by partial tumor irradiation sparing the peritumoral immuneenvironment, and consequent shifting of immune-suppressive to immune-stimulatory effect. This would improve the radiation-directed tumor cell killing, adding to it a component of immunemediated killing. Our preclinical findings showed that the high-single-dose irradiation of hypoxic tumor cells generates a stronger bystander effect (BE) and AE than the normoxic cells, suggesting their higher “immunogenic potential”. This led to the development of a novel Stereotactic Body RadioTherapy (SBRT)-based PArtial Tumor irradiation targeting HYpoxic segment (SBRT-PATHY) for induction of the immune-mediated BE and AE. Encouraging SBRT-PATHY-clinical outcomes, together with immunohistochemical and gene-expression analyses of surgically removed abscopaltumor sites, suggested that delivery of the high-dose radiation to the partial (hypoxic) tumor volume, with optimal timing based on the homeostatic fluctuation of the immune response and sparing the peritumoral immune-environment, would significantly enhance the immune-mediated anti-tumor effects. This review discusses the current evidence on the safety and efficacy of SBRT PATHY in the treatment of unresectable hypoxic bulky tumors and its bystander and abscopal immunomodulatory potential.

Original languageEnglish
Article number50
Pages (from-to)1-20
Number of pages20
JournalCancers
Volume13
Issue number1
DOIs
Publication statusPublished - Jan 2021

Keywords

  • Abscopal effect
  • Bystander effect
  • Immune-microenvironment
  • Partial irradiation
  • SBRT
  • Timing

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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