Introduction: Hypo-fractionated radiotherapy (HFRT) regimens can induce immune system activation and help to identify a therapeutic window after RT by measuring cytotoxic T-cell concentration. Here, we summarise previous preclinical and clinical studies on the effects of HFRT on the immune system, both locally and systemically. We also investigate the existing data on the optimal dose and fractionation scheme of HFRT to enhance local and distant anti-tumour immunity.

Methods: A search was conducted using the PubMed, ScienceDirect, and Google Scholar databases. The systematic review was conducted in accordance with the PRISMA-DTA guidelines. Quality was assessed utilising the Prediction model Risk Of Bias ASsessment Tool (PROBAST). Data from publications that met quality criteria were grouped via (1) hypo-fractionated radiotherapy, (2) CD8+ T-cells infiltration, (3), immune stimulation, and (4) abscopal effect.

Results: After eligibility consideration, 12 studies (7 = preclinical and 5 = clinical) were selected for this systematic review article. Ten of the 12 studies observed T-cell infiltration into the tumour environment following HFRT. Moreover, six of 12 preclinical and clinical studies tested the HFRT schemes with several-day intervals to control tumour growth. To assess the possible immunogenic impact of HFRT on the immune system both locally and systemically, eight previous studies examined the abscopal effect (AE) and response rates following optimal HFRT schedules.

Conclusions: Existing literature suggests that HFRT with an optimal regimen can induce the activation of T lymphocytes and break tumour tolerance while simultaneously reducing the frequency of Tregs. The collected studies also suggested that optimal dosages and fractions of HFRT induce an immune response. However, it should be further explored to provide clinicians with information that would be valuable when making decisions regarding patient care. This strategy may simplify protocols, increase cancer patients’ response rate to treatment, lower costs, and lower their chance of toxicity and developing immune-related side effects after receiving chemotherapy and immunotherapy.