Synergizing Local and Systemic Therapies: Advances in Abscopal Effect-Based Strategies for Advanced Cancer

Corresponding author: Zhanglin, stepinghuns2@163.com

DOI: 10.12201/bmr.202606.00053

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  Abstract: Background: The abscopal effect, defined as tumor regression at non-irradiated or non-treated distant sites following localized therapy, represents a paradigm-shifting phenomenon in oncology with the potential to achieve "functional cure" in advanced cancers. However, spontaneous or single-modality abscopal responses remain exceedingly rare, occurring in fewer than 10% of patients across most solid tumor types. Objective: This review systematically examines the synergistic framework of "local induction plus systemic enhancement" in driving abscopal effects, encompassing the underlying immunological mechanisms, clinical evidence, and translational prospects. Methods: We conducted a comprehensive literature search of PubMed and Web of Science databases (2015–2026), focusing on stereotactic body radiotherapy (SBRT), oncolytic viruses (OV), and interventional therapies as "inducers," and immune checkpoint inhibitors (ICI), immune-modulating chemotherapy, anti-angiogenic agents, and immune effector cell therapies (CAR-T/TCR-T) as "enhancers." Results: All three inducer modalities activate innate immunity through immunogenic cell death (ICD), yet single-agent abscopal rates remain below 15%. Upon combination with enhancers, SBRT plus ICI demonstrates the most robust evidence (abscopal rates 20–35%), while OV plus ICI shows efficacy in ICI-resistant populations (STOMP trial: 75% clinical benefit). Immune effector cell therapies, particularly CAR-T/TCR-T, represent the next-generation enhancers capable of overcoming solid tumor infiltration barriers when empowered by local treatments, with preclinical data demonstrating macrophage- and T cell-mediated abscopal responses following sCAR-T plus microwave ablation or OV plus CAR-T combinations. Conclusion: The "local induction plus systemic enhancement" framework represents a promising and evidence-supported strategy for achieving abscopal effects in clinical practice. ICI serves as the most universally applicable "accelerant," whereas CAR-T/CAR-NK/TCR-T therapies embody a highly promising future direction. Individualized decision-making based on MSI status, antigen heterogeneity, and treatment line remains the cornerstone of successful clinical translation.

  Key words: Abscopal effect; stereotactic body radiotherapy; oncolytic virus; interventional therapy; immune checkpoint inhibitor; CAR-T; combination therapy

  Submit time: 23 June 2026

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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  1	2026-06-15	10.12201/bmr.202606.00053V1	Download

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