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4.3 Radio immunotherapy (RIT) 81

FIGURE 4.6 The abscopal effect.

4.3.1.1 Radiotherapy and its effect on the immune system
As noted in the previous section, radiotherapy destroys the tumor locally, and this is
done by destruction the DNA. Along with this local action that destroys the DNA of
tumor cells, radiotherapy can cause changes in the immune response against cancer
antigens [28]. Significantly, radiotherapy works not only against a localized irradi-
ated tumor, but also against nonirradiated tumor that is created by metastasis at a
distance from the primary tumor. This phenomenon is called abscopal and was intro-
duced for the first time by Mole in 1953 [29]. The abscopal effect is schematically
shown in Fig. 4.6.
As shown in Fig. 4.6, in the interpretation of the abscopal effect, the radiation
generates tumor associated antigens (TAAs). These TAAs are then identified by
APCs such as DCs and connected to them. This connection is made by the major
histocompatibility complex class 1 (MHC-1), and DCs introduce TAAs to T cells
in this way. Another consequence of radiotherapy is the activation and maturation
of DCs which occurs when damage-associated molecular patterns (DAMPs) such as
uric acid, ATP, high-mobility group box 1 (HMGB1), heat shock protein, IL-1α and
hyaluronic acid are released and detected by Toll-like receptors (TLRs) at the surface
of DCs [30]. In addition to the beneficial effects that radiotherapy has on stimulat-
ing the immune system to fight cancer cells, it also has inhibitory effects on immune
system. For example, radiotherapy can increase regulatory T-cells (T cells) in the
reg
tumor microenvironment and accumulation of T cells in that microenvironment
reg
and secretion of some cytokines such as IL-10 and TGFβ can inhibit myeloid-derived
suppressor cells (MDSCs) [31]. Therefore, in contrast to the beneficial stimulatory