Radiotherapy, photodynamic therapy, and cryoablation‐induced abscopal effect: Challenges and future prospects

• Published in: Cancer innovation (Print) Vol. 2; no. 5; pp. 323 - 345
• Main Authors: Ali Mohammad, Sadik, Hak, Arshadul, Pogu, Sunil V., Rengan, Aravind K.
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.10.2023; John Wiley and Sons Inc; Wiley
• Subjects: abscopal effect; Adenosine triphosphate; Antigens; Apoptosis; cancer; Cancer therapies; Case reports; Cell death; Chemotherapy; Combination therapy; cryoablation; Cytotoxicity; Endoplasmic reticulum; Immunotherapy; Ligands; local therapy; Lymphocytes; Lymphoma; Metastasis; Photodynamic therapy; Radiation therapy; radiotherapy; Review; Tumor necrosis factor-TNF; Tumors; local therapy; cryoablation; photodynamic therapy; immunotherapy; radiotherapy; cancer; abscopal effect
• ISSN: 2770-9191; 2770-9183; 2770-9183
• DOI: 10.1002/cai2.53

Local therapy modalities such as radiation therapy, photodynamic therapy, photothermal therapy, and cryoablation have been used to treat localized tumors for decades. The discovery of the abscopal effect causes a paradigm shift where local therapy also causes systemic effects and leads to the remission of nonirradiated tumors. The abscopal effect of radiation therapy, alone or in combination with other treatments, has been extensively studied over the last six decades. However, the results are unsatisfactory in producing robust, reproducible, and long‐lasting systemic effects. Although immunotherapy and radiation therapy are promising in producing the abscopal effect, the abscopal effect's mechanism is still unclear, owing to various factors such as irradiation type and dose and cancer type. This article reviews the research progress, clinical and preclinical evidence of the abscopal effect by various local therapies alone and in combination with chemotherapy and immunotherapy, case reports, and the current challenges in producing the abscopal effect by various local therapies, focusing on radiotherapy, photodynamic therapy, cryoablation, and the prospects for obtaining a robust, reproducible, and long‐lasting abscopal effect. Primary or local tumor ablation following local therapy (such as radiotherapy, photodynamic therapy, and cryoablation) causes the release of damage‐associated molecular proteins and tumor‐associated antigens, which are then presented to dendritic cells (antigen‐presenting cells) and results in the development of a systemic antitumor immune response, or “abscopal effect.” However, the immune‐suppressive tumor microenvironment blocks the antitumor immune response through several mechanisms, including the immune checkpoint mechanism (programmed death‐1, programmed death ligand‐1, and cytotoxic T lymphocyte‐associated protein‐4) and the overexpression of immunosuppressive cells myeloid‐derived T‐regulatory cells, myeloid‐derived suppressor cells, and tumor‐associated macrophages, and so on. The use of immunotherapy can be used to treat these immune suppression mechanisms. Therefore, local therapy and immunotherapy combined have been proven to provide an effective abscopal impact. Immune‐related adverse effects, however, can result from immunotherapy. Determining the precise sort of immunosuppressive mechanism and using specialized immunotherapy can combat these drawbacks. This can be achieved by using a nanotheranostic method, in which nanoparticles are loaded with prognostic biomarkers and predictive biomarkers, and to develop a strategy that could be multifaceted and address all potential obstacles that slow the abscopal impact.