Table 1 Recent studies on the mechanisms of hypoxia-driven crosstalk between tumor cells and TAMs

Non-small-cell lung carcinoma

TAMs

Exosomal miR-101

CDK8

Downregulated exosomal miR101 induces the secretion of IL1A and IL6 in macrophages and leads to inflammation in TME

[80]

Glioma

TAMs

Exosomal miR-1246

STAT3 and NF-κB

Promote M2-like macrophage polarization; promote tumor proliferation, migration and invasion

[81]

Multiple myeloma

TAMs

Exosomal miR-1305

Unknown

Promote M2-like macrophage polarization;

[82]

Epithelial ovarian cancer

TAMs

Exosomal miR-21–3p, miR-125 b-5p and miR-181 d-5p

SOCS4/5/STAT3

Promote M2-like macrophage polarization; promote tumor proliferation and migration

[83]

Endometrial cancer

TAMs

Exosomal miR-21

Unknown

Promote M2-like macrophage polarization

[84]

TAMs

epithelial ovarian cancer

Exosomal miR-223

PTEN-PI3K/AKT

Decrease apoptosis rate, increase cell viability, and enhance drug resistance

[85]

Pancreatic Cancer

TAMs

Exosomal miR-301a-3p

PTEN/PI3Kγ

Promote M2-like macrophage polarization; promote pancreatic cancer cells migration, invasion, and EMT

[86]

Glioma

TAMs

Exosomal IL-6 and miR-155-3p

IL-6-pSTAT3-miR-155-3p-autophagy-pSTAT3

Induce autophagy and M2-like polarization in macrophage; promote tumor proliferation and migration

[87]

Epithelial ovarian cancer

TAMs

Exosomal miR-940

Unknown

Promote M2-like macrophage polarization; promote tumor cell proliferation and migration

[88]

Esophageal Squamous Cell Carcinoma

TAMs

Exosomal Hsa-circ-0048117

miR-140/TLR4

Function as a ceRNA; promote M2-like macrophage polarization; promote tumor invasion and migration

[89]

Hepatocellular carcinoma

TAMs

Exosomal HMMR-AS1

miR-147a/ARID3A

Function as a ceRNA; promote M2-like macrophage polarization; promote tumor proliferation and growth

[90]

Melanoma

TAMs

Exosomal Let-7a miRNA

Insulin-Akt-mTOR

Recruit macrophages, promote M2-like polarization and enhance mitochondrial OXPHOS in macrophage

[91]

Non-small-cell lung cancer

TAMs

Exosome

HIF-1α

Upregulate PD-L1 in macrophage

[92]

Breast tumor

TAMs

OSM

mTORC2-Akt1

Promote M2-like macrophage polarization

[93]

TAMs

Gastric cancer

CXCL8 (IL-8)

CXCR1/2-JAK/STAT1

Deteriorate the GC malignant phenotype; promote IL-10 expression in tumor; IL-10 activates the macrophage IL-10/ NF-κB signaling pathway and induce M2 polarization

[94]

Cervical cancer

TAMs

CCL8

ZEB1–CCL8-CCR2–NF-κB

Enhance TAM migration

[95]

Lung cancer

TAMs

MCP-1 (CCL2)

NF-κB/HIF-1α

Recruit macrophages

[96]

Head and neck squamous cell carcinoma

TAMs

VEGF and IL-6

Unknown

Recruit and polarize macrophages

[97]

TAMs

Head and neck squamous cell carcinoma

CCL15

CCR1-NF-κB

Promote tumor tolerance to gefitinib

[97]

TAMs

Gastric Cancer

VEGF

PI3K-Akt and p38 MAP kinase

Promote the proliferation and invasion of cancer cell

[98]

Lewis lung carcinomas

TAMs

Sema3A

Nrp1/VEGFR1/PlexinA1/A4

Attract macrophages to the hypoxic region

[99]

Hepatocellular carcinoma

TAMs

MYDGF

Unknown

Enhance macrophage chemotaxis and inflammatory cytokines release, such as IL-6 and TNF-α; enhance self-renewal of cancer stem cells; promote tumor angiogenesis

[100]

TAMs

Breast cancer

Gal‐3

NF-κB via ROS

Promote tumor growth, metastasis, angiogenesis; enhance VEGFA secretion and glucose consumption in macrophage

[101]

Hepatocellular carcinoma

TAMs

HMGB1

Unknown

Exacerbate infiltration, M2-like polarization and IL-6 expression of macrophages; promote tumor EMT

[102]

TAMs

Breast tumor

Spint1

HIF-2α–Spint1/HGFA HGF/c-Met

Inhibit the proliferation of tumor cell

[103]

TAMs

Colon Cancer

SIRPα

SIRPα-CD47

Increase macrophage phagocytic activity

[104]

Cervical cancer

TAMs

Nrp-1

Unknown

Recruit and polarize macrophages towards the M2 phenotype

[105]

Hepatocellular carcinoma

TAMs

Cellular debris

TLR4/TRIF/NF-κB

Polarize macrophages into M2 type and promote the secretion of IL-1β

[106]

TAMs

Hepatocellular carcinoma

IL-1β

IL-1β/HIF-1α/COX-2

Enhance EMT of tumor cells

[106]

Lewis lung carcinoma and B16-F1 melanoma

TAMs

Lactic acid

HIF-1α

Induce the expression of VEGF and the M2-like polarization of TAMs

[107]

Lung Cancer

TAMs

Lactic acid

Unknown

Differentially affect TAM subset metabolism; trigger the T-cell suppressive capacity of TAMs

[108]

Lung Cancer

TAMs

Succinate

SUCNR1

Promote macrophage recruitment, migration and M2-skewed phenotype; M2 macrophages secret IL-6 to enhance cancer cell migration; induce cancer cell migration and EMT

[109]