Predicting the Abscopal Effect: Associated Tumor Histologic Subtypes and Biomarkers

Blessie Elizabeth Nelson, Jacob J. Adashek, Aakash Akshay Sheth, Vivek Subbiah

Radiotherapy is a pillar of cancer treatment, which has historically been used primarily to treat localized disease with curative intent. With the increasing role of radiotherapy for metastatic disease and rapid integration of immunotherapy into the standard of care for various cancers, it has been observed that local radiation to one malignant site can lead to shrinkage of tumors at other sites, a phenomenon termed the "abscopal effect." Historically, there was little mechanistic elucidation as to how this phenomenon occurs. However, multiple groups have recently identified associated immuno-prognostic factors, such as high post-radiotherapy absolute lymphocyte count, neoantigens, myeloid-derived suppressor cells, and NK cells. The concomitant use of immunotherapy with radiotherapy has been documented to induce the abscopal effect. As immunotherapies continue to be incorporated into most cancer treatment approaches, understanding which patients are more likely to benefit from an abscopal effect may allow for optimization of both systemic and radiotherapeutic strategies. This review highlights the tumor histologic subtypes and biomarkers of the greatest utility for the recognition and identification of patients likely to benefit from the abscopal effect.