Secretion of TAMs and autophagy
TAMs can secrete various immunosuppressive molecules, such as IL-10,
TGF-β, and prostaglandin E2 (PGE2), into TME, which results in the
induction of immunosuppressive Tregs and facilitates T cell suppression
and further suppress antitumor immunity[75]. Based
on the secretion of various growth factors, cytokines, chemokines, and
extracellular vesicles, TAMs can exert antitumor immune effects and
immunosuppressive effects through multiple
pathways[76, 77]. Certain substances secreted by
TAMs promote autophagy in tumor cells. Research showed that M2
macrophages would secrete IL-17 to stimulate chaperon-mediated autophagy
in tumor cells to help them avoid apoptosis[50].
Ni[78] et al. indicated that GDNF secreted by TAMs
can regulate lysosomal function and autophagic flux through the
GDNF-GFRA1 axis to enhance autophagy levels in GC cells, thus helping
TAM colonization and survival in the metastasis. TAMs-exosome H19,
because of the increased LC3-II expression and decreased levels of p62,
significantly enhanced the autophagy of BC cells by stabilizing the
expression of ULK1[79]. This suggests that the
secretion of TAMs contained the regulatory effector of autophagy process
in cancer cells. The activation of autophagy in TAMs promotes the
secretion of inflammatory cytokines and thus increases the
tumor-associated inflammatory response, aiding tumor
progression[61]. Wang[80] et
al. found that induction of autophagy in TAMs, promoting TGF-β1
secretion through the FUT4/p-ezrin pathway and induced EMT in
co-cultured lung adenocarcinoma cells. However, some cargo proteins can
be secreted through autophagy[25, 26]. For
example, Gal-1, a soluble pro-tumor factor widely expressed in TAMs.
TAMs can regulate Gal-1 secretion via TLR2-mediated secretory autophagy
to facilitate HCC growth in mice and correlates with the poor prognosis
of HCC patients[81]. In summary,
Autophagy-regulated TAM can promote tumorigenesis and progression by
mediating interactions with tumor cells through autocrine or paracrine,
activating inflammatory cells, disrupting cytokine networks, and evading
immune surveillance.