Infiltration of TAMs and autophagy
High infiltration of TAM usually has a poor prognosis in most human
tumor diseases[55]. It has been shown that the
infiltration of immune cells into tumors is orchestrated by cytokines
and chemokines released from the tumor microenvironment acting in
autocrine and/or paracrine manner(s), thus facilitating the
communication between several types of cells within the TME in order to
control and shape tumor growth[56]. Among them,
TAMs, as the main tumor-infiltrating immune cell population, are usually
induced as ”accomplices” by tumor cells to promote tumor immune escape,
angiogenesis, tumor growth and metastasis[57]. It
was demonstrated that inhibition of tumor-associated macrophages-induced
autophagy in hepatocellular carcinoma enhances the cytotoxicity of the
chemotherapeutic agent oxaliplatin against hepatocellular carcinoma
cells[58]. F. nucleatum was found to be a
major oncogenic bacterium that drives TAMs formation and induces
infiltration. The main mechanisms are manifested in, F. nucleatumwas able to bind to membrane proteins on the surface of OSCC cells to
activate autophagy, leading to GLUT1 aggregation in the plasma membrane
and extracellular lactate deposition, thereby increasing extracellular
acidification and M2-like TAM formation. Inhibition of both autophagy
signaling and GLUT1 can effectively reduce the formation of TAMs and
inhibit the progression of OSCC cells[49, 59].
This provides a theoretical basis to further investigate the complex
relationship between TAM infiltration, autophagogenesis, and tumor cell
development. Notably, one study found that high M1 macrophage
infiltration correlated with better treatment profiles in cancer
patients. Increased secretion of the pro-inflammatory factors CCL5 and
CXCL10 in TME of melanoma and CRC tumor cells when induced with the
autophagy inhibitor VPS34 inhibitor (SB02024 or SAR405), which in turn
promoted major immune effector cells (NK cells, CD8+T
and CD4+T cells, DC cells and M1 macrophages)
infiltration increased, and thus reversed resistance to anti-PD-1/PD-L1
therapy in melanoma and colorectal cancer tumor
models[60]. In summary, these studies suggest that
autophagy exerts a pro- or oncogenic effect on the accumulation of TAMs
in TME, but the interaction between autophagy and the infiltration of
such cytotoxic effector immune cells is largely understudied.