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5.2 Innate cell-based therapy 121

Table 5.2 Some of the cytokines and transcription factors expressed by
ILCs.

Innate lymphoid cells Secreted cytokines Expressed transcription factors
NK cells IFNγ, TNF T-bet, EOMES
ILC1s IFNγ, TNF T-bet
ILC2s IL-5, IL-9 and IL-13 GATA3
ILC3s IL-22 and/or IL-17A RoRγt

5.2.2 Innate lymphoid cells
As mentioned in the preceding section, ILCs are cells of the innate immune system
that derived from lymphoid progenitors in the bone marrow. These cells are divided
into five groups based on the cytokines they secreted and also on the expression of
their transcription factors. For instance, IFNγ is a cytokine secreted by NK cells and
also T-bet that expressed by this type of cells. Some of the secreted cytokines and
transcription factors expressed by ILCs are summarized in Table 5.2.
In recent years, researchers have focused on ILCs due to the cell surface mol-
ecules expressed or secreted by these cells and their ability to counteract tumors.
In this regard, studies have shown that NK cells induce immune responses through
the release of various cytokines and chemokines and also have cytotoxicity to tumor
cells. Although in the context of cancer treatment, more attention has been paid to
NK cells, non-NK cell ILCs can also play a role in the fight against tumors due to
the tumor microenvironment and the components of cytokines secreted in the tumor
environment [22]. For example, in 2014, Mirchandani and colleagues have examined
the similarities and effect of ILC2s and T cells on each other; the results of this study
have shown that ILC2s by expressing MHC class II, introduce antigens to the adap-
tive immune system and induce T cell responses against antigens [23]. Or in another
study conducted in 2018, the results have shown that in an animal model of mice
lacked ILC2s genetically, the tumor growth rate and metastasis was increased dra-
matically; and the authors attributed this increase in tumor growth rate in the absence
of ILC2s to IL-13 secretion by ILC2s, that induces cytotoxic T cell responses [24].
Although based on the researches demonstrating the effect of non-NK cell ILCs on
stimulation of the adaptive immune system against antigens, their precise effect on
cancer resistance is still unclear. And the main focus in this area is on NK cells.

5.2.3 NK cells
NK cells make up about 15% of blood lymphocytes. Morphologically they are simi-
lar to B and T lymphocytes but NK cells are larger and more granular. And most
importantly, unlike T cells and B cells, they lack diverse antigen-specific receptors
(TCR and BCR). The granules of these cells contain cytolytic proteins such as per-
forin and granulysin which give them cytotoxicity. In addition, like other ILCs, NK
cells are capable of producing various chemokines and cytokines such as IFNγ and