부산대학교 도서관

Abscopal effect as a stimulator of immune system in combination with immunotherapy. Increase in antigen presentation following higher ratio of immunologic cell death within TME can amplify anti-tumor immunity via release of chemokines, activation of DCs, triggering CTLs to infiltrate into TME and stimulation of CD4+ to proliferate to CTLs and NK cells. • High doses of radiotherapy such as SBRT triggers abscopal effect which is associated with infiltration of CTLs and NK cells. • The combination of immunotherapy with abscopal effect of radiotherapy prolongs anti-tumor immunity within tumor. • Dual or multiple targeting of immune checkpoints amplifies abscopal effect induced by radiotherapy for longer times. • Depletion of Tregs and M2 macrophages can enhance tumor suppression by radioimmunotherapy. Abscopal effect is an interesting phenomenon in radiobiology that causes activation of immune system against cancer cells. Traditionally, this phenomenon was known as a suppressor of non-irradiated tumors or metastasis. However, it can be used as a stimulator of the immune system against primary tumor during radiotherapy. Immunotherapy, a novel tumor therapy modality, also triggers immune system against cancer. To date, some immunotherapy types have been developed. However, immune checkpoint blockade is a more common modality and some drugs have been approved by the FDA. Studies have shown that radiotherapy or immunotherapy administered alone have low efficiency for tumor control. However, their combination has a more potent anti-tumor immunity. For this aim, it is important to induce abscopal effect in primary tumors, and also use appropriate drugs to target the mechanisms involved in the exhaustion of cytotoxic CD8+T lymphocytes (CTLs) and natural killer (NK) cells. Among the different radiotherapy techniques, stereotactic body radiation therapy (SBRT) with some few fractionations is the best choice for inducing abscopal effect. On the other hand, programmed cell death 1 (PD-1) is known as one of the best targets for triggering anti-tumor immunity. This combination is known as the best choice among various strategies for radioimmunotherapy. However, there is the need for other strategies to improve the duration of immune system's activity within tumor microenvironment (TME). In this review, we explain the cellular and molecular mechanisms behind abscopal effect by radiotherapy and evaluate the molecular targets which induce potent anti-tumor immunity. [ABSTRACT FROM AUTHOR]