The Abscopal effect is termed for the theory that describes why sometimes using a local treatment in one area of metastatic cancer (such as radiation therapy) may result in cancer shrinkage in some other untreated area. While this phenomenon was seen as a rare occurrence in the past, it has become more frequent with the arrival of immunotherapy drugs such as checkpoint inhibitors to treat cancer. R.H. Mole was the first person who proposed the term “Abscopal” in which the single word ‘Ab’ means ‘away from something,’ and the other half ‘Scopus’ means ‘target’. He gave the term in 1953 referring to the effects of the ionizing radiation from a distance that is away from the volume that is irradiated but lies somewhere within the same organism.

The Abscopal effect is a phenomenon that lies in the treatment of metastatic cancer where the shrinkage of the untreated tumors takes place simultaneously with the shrinkage of the tumors within the area of the localized treatment. Here metastatic cancer means the spread of cancer or the cancerous agent from an initial or the primary site to a different or secondary site within the body of the same host.

HISTORICAL REFERENCE

Initially it was the localized Radiation therapy that was associated with the single-tumor, now the term “Abscopal effect” has also come up that constitute other types of localized treatments as well. These include treatments such as electroporation and intra-tumoral injection of therapeutics. However, the term Abscopal effect should only be used when the used local treatments result in some systemic effects. For example, where the chemo-therapeutics commonly circulate throughout the bloodstream and therefore reduces the possibility of any Abscopal effect in the body of an individual.

The mediators or drugs that are used in the Abscopal effect of radiotherapy were not known for many decades. Around 2004, it was postulated for the first time that the immune system might be responsible for these anti-tumor effects in off-target regions of the body. The various studies in animal models of skin cancer, mammary, and colorectal tumors have supported or shown this hypothesis. The Abscopal effects that are caused due to an immune system that is, they are immune-mediated, were also described in patients who had metastatic cancer.

BIOLOGICAL EXPLANATIONS

Just like the interaction between antigens and antibodies and the immune reaction against antigens from the bacteria or viruses, the Abscopal effect requires the interaction between an antigen and the helper T cell (this is also known as priming) or the immune cells to become active against the tumor antigens. when a tumor nodule is irritated locally then and it mainly to do some forms of tumor cell death that are immunogenic and this, in turn, liberates tumor-derived antigens. These antigens can easily be recognized and processed by the antigen that presents the cells within the tumor.  Cytotoxic T cells are the cells that help to recognize the tumor antigens. These cells may in turn be further primed by the tumor cells that are presenting the antigen.

If we compare the effect of the local irradiation on the tumor cells, these cytotoxic T cells effectively circulate through the bloodstream and hence can destroy the remaining tumor cells in other parts of the body which were not locally irradiated. In the same way the increase in tumor-specific cytotoxic T cells was shown to correlate with the Abscopal anti-tumor responses in various patients.

INFLUENCING FACTORS

Abscopal effects of the ionizing radiations are often blocked by the micro-environment that is immuno-suppressive held inside the irradiated tumor which further prevents effective T cell priming. The micro-environment is the tumor micro-environment situated around a tumor which includes the surrounding blood vessels, immune cells, fiber cells, other molecules, and other matrix material. This fact fully explains why the effect is so rarely seen in patients who receive radiotherapy only. Radiotherapy is such a treatment that is used to achieve the local control of the tumor irradiated area. As we know that there may also be a tumor-induced response in those areas where radiotherapy has not been performed which is stated as the Abscopal effect of radiotherapy, but still the whole biological mechanism under this effect is not clearly understood.

There are many direct and indirect effects of radiation on deoxyribonucleic acid. The direct and indirect effects are the mechanism that is mainly responsible for the cytotoxic effects of radiotherapy. There may also be effects that are considered the direct cytotoxic effects on tumor cells, the impacts on the immune system have also been a great subject of studies by doctors since long. These effects upon the immune system might result in an immune-mediated anti-tumor response.

CONCLUSION

Radiotherapy is one of the most important cornerstones in the treatment of cancer in a definitive way and with well-established local effects. If we study the classical radio-biology postulates, we will see that the toxic effects from which a cell may suffer because of radiation are the result of direct DNA damage and indirect generation of the free radicals that cause cell damage. Some research has also shown that radiotherapy also causes localized bystander effects. In this effect the treated tumor cells start to influence neighboring cells. Because of all these cytotoxic effects of it and also due to the effects on circulating lymphocytes radiotherapy is also known as the immuno-suppressant, but if we see by the definition of the Abscopal effect, there might be an immune stimulant effect of the radiotherapy.

The Abscopal effect is seen as a rare event. Over the years some of the Abscopal effect events were published in some case study reports. Abuodeh, a biologist, also reviewed the theory and reported that around 46 case reports were published where the Abscopal effect was observed from radiotherapy only. When we take a close look at the reviewed cases, we can understand that some of the Abscopal effects were observed independently from the treatment dose, fractionation, modality, and the characteristic of the target lesion.

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