Nanotechnology‐enhanced radiotherapy and the abscopal effect: Current status and challenges of nanomaterial‐based radio‐immunotherapy

Abstract

Rare but consistent reports of abscopal remission in patients challenge the notion that radiotherapy (RT) is a local treatment; radiation‐induced cancer cell death can trigger activation and recruitment of dendritic cells to the primary tumor site, which subsequently initiates systemic immune responses against metastatic lesions. Although this abscopal effect was initially considered an anomaly, combining RT with immune checkpoint inhibitor therapies has been shown to greatly improve the incidence of abscopal responses via modulation of the immunosuppressive tumor microenvironment. Preclinical studies have demonstrated that nanomaterials can further improve the reliability and potency of the abscopal effect for various different types of cancer by (1) altering the cell death process to be more immunogenic, (2) facilitating the capture and transfer of tumor antigens from the site of cancer cell death to antigen‐presenting cells, and (3) co‐delivering immune checkpoint inhibitors along with radio‐enhancing agents. Several unanswered questions remain concerning the exact mechanisms of action for nanomaterial‐enhanced RT and for its combination with immune checkpoint inhibition and other immunostimulatory treatments in clinically relevant settings. The purpose of this article is to summarize key recent developments in this field and also highlight knowledge gaps that exist in this field. An improved mechanistic understanding will be critical for clinical translation of nanomaterials for advanced radio‐immunotherapy.This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

Immunotherapy of Diseases and Nanotechnology: Current State and Prospects

“…DAMP provide the "eat me" signals for antigen recognition and phagocytosis by DC and trigger the activation of the adaptive immune response [53]. More importantly, ICD-derived tumor antigens can be controlled by the immune system and pose threat to abscopal and metastatic tumors, which is called the "abscopal effect" [51,54].…”

A pH-Sensitive Nanoparticle as Reactive Oxygen Species Amplifier to Regulate Tumor Microenvironment and Potentiate Tumor Radiotherapy

“…As a local treatment for tumors, RT may be ineffective in addressing metastasized tumors owing to a lack of adequate immune response in clinical practice. [21][22][23][24] Fortunately, emerging evidence suggests that RT could activate the stimulator of STING pathway that acts as an innate immune signaling to induce the antitumor immune response against tumor cells when damaged tumor DNA escapes from the nucleus to the cytosol. [25][26][27][28] This discovery has opened up new possibilities for the clinical use of RT.…”

Dual effects of radiotherapy on tumor microenvironment and its contribution towards the development of resistance to immunotherapy in gastrointestinal and thoracic cancers

“…The favorable effects of radiotherapy deliver a rationale for the combined therapeutic strategy. Application of complex treatment methods, including the use of radiotherapy as an activator of internal anti-cancer mechanisms in support of chemotherapy and immunotherapy, is recommended ( Zhang et al, 2023b ; Pontoriero et al, 2023 ; Shannon et al, 2023 ; Viswanath et al, 2023 ). In this study, we discuss the role of radiotherapy in the regulation of TME-related cancer-promoting effects.…”