The immune system is the body's natural defense system; provides protection against diseases; It recognizes and destroys invading microorganisms and tumor cells formed in tissues. The science that studies the immune system is called immunology.
The purpose of cancer immunotherapy is to stimulate the person's own immune system against the tumor. Because cancer cells are different from the body's normal cells, they can be recognized and destroyed by the immune system. However, cancer cells that have the potential to masquerade as normal cells may escape the immune system, or the response may not be sufficient to completely get rid of cancer cells. At this point, immunotherapies activate our immune system, allowing cancer cells to be recognized and destroyed. This can be achieved by external administration of antigens that will stimulate the immune response, or by immune regulation (modulation) with vaccines or oncolytic viruses.
The first studies on immunotherapy were performed on melanoma and renal cell carcinoma. It was made with alpha and interleukin-2 (1). The superiority of Sipuleucel-T, a type of cancer vaccine, over placebo was demonstrated in a study conducted in patients with metastatic castration-resistant prostate cancer (2). In recent years, successful results have begun to be obtained, especially in studies on PDL-1 and PD-1 (3-6).
Radiotherapy is a local (regional) form of treatment, affecting the cells where it is applied. It causes DNA damage and therefore it is expected to show its effect where it is applied. However, the defined “abscopal effect” indicates that radiotherapy can also have its effect in areas far from where it is applied. This effect was first described by Mole in 1953 (7). In this word, which is of Latin origin, "ab" means distant settlement and "scopus" means target. The first types of cancer in which the abscopal effect was described were; renal cell carcinoma, lymphoma, leukemia, neuroblastoma, breast and melanoma.
Although the mechanism of this effect is not fully understood, it has been suggested that it may be through immunological mechanisms. If administered at an effective dose, radiotherapy can act as a tumor vaccine (release of tumor-specific antigen). , increasing MHC-I expression, increasing FasL expression) or causing immunological cell death.
The appropriate radiotherapy dose and technique are still under research. Although there are studies showing that the abscopal effect increases when high-dose radiotherapy is applied, as in radiosurgery or hypofractionated treatments, there are also studies claiming that periodic application of 1.8-2 Gy in fractionated radiotherapy suppresses immune cells more (8).
Another question that needs to be answered is whether it is possible to increase this effect, especially when used together with immune-regulating agents or chemotherapy. A study showing that definitive chemoradiotherapy has a systemic immunological effect was presented at the Multidisciplinary Head and Neck Cancers Congress held in the USA this year (9). In a study conducted on seventeen head and neck cancer patients, it was found that the levels of some cytokines as well as T cells increased during treatment. One of the most striking results with combinations of radiotherapy and immunotherapy was reported by Postow et al. It was reported by (10). In this study, when radiotherapy was applied to one of the metastases of the patient who had progressed while under ipilumumab treatment, it was observed that there was a significant regression in both this mass and the metastases outside the radiotherapy area. In another study, it was reported that when radiotherapy was applied to liver metastases in a patient with metastatic lung adenocarcinoma resistant to chemoradiotherapy, there was a significant response in both these metastases and distant metastases (11). However, it should not be forgotten that most of the studies conducted with immunotherapy are in metastatic diseases.
There is more and more data showing that radiotherapy, when used together with chemotherapy or immunotherapeutic agents, creates not only local but also systemic effects. It seems that it will be possible to use radiotherapy and immunotherapy more in the clinic once questions such as appropriate dose and technique are answered.
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