Cancer
Immunological memory has also been established to play a central role in
tumor progression. For example, β-glucan-induced mouse granulocyte
immune memory is reportedly associated with diminished tumor growth,
with this anti-tumor effect being attributed to a reprogramming of
neutrophils toward an anti-tumor phenotype, a process dependent on type
I interferon signaling, although independent of host adaptive immunity67. Indeed, innate immune cells may play opposing
roles by displaying both tumor-suppressing and tumor-promoting
properties. For example, in terms of suppression, BCG treatment has long
been known to eradicate malignancies such as bladder cancer and melanoma
and reduce the risk of leukemia and lymphoma 68-71.
Furthermore, β-glucan has also been used in clinical trials for cancer
therapy such as that for non-small cell lung, breast, and colorectal
cancers 72. The findings of further studies have
revealed that such anti-tumor effects may be attributable to the
non-specific protection triggered by epigenetic reprogramming and is
associated with the induction of monocyte/macrophage memory31, 73.
With respect to the tumor-promoting effects of macrophage memory,
tumor-associated macrophage (TAM), which serves as important immune
regulatory element in tumor progression, has been shown to be involved
in the development of an immunosuppressive tumor microenvironment and
facilitate tumor immune escape, growth, and metastasis74, 75. The salient feature of TAM differentiation is
epigenetic reprogramming involving histone modification, such as H3K4me3
and H3K9me3 alterations in the promoter regions of IL-6 and TNF-α,
thereby inducing the production of pro-inflammatory cytokines and
expression of tumor-associated gene profiles 76. For
example, predominant functional changes in thyroid cancer (TC)-induced
macrophage memory enhance inflammatory properties and the modification
of cell metabolism. This functional reprogramming has been established
to be partially mediated by TC-derived lactate via AKT1/mTOR-dependent
aerobic glycolysis, resulting in long-term epigenetic modifications at
histone methylation levels, such as H3K4me3 and H3K9me3 in the promoters
of IL-6 and TNF-α, thereby leading to increases in the expression of
genes characteristic of cancer tumor profiles, and an increase in the
production of TAM pro-inflammatory factors 76, 77.