Table 1 The interaction of exosomes between different cells in TME of lung cancer

macrophages

let-7a-5p

/

A549

BCL2L1

Induced A549 lung cancer cell death and altered expression of MYC, EGFR, and Vimentin

[14]

A549

let-7a

Hypoxia

Macrophages

Insulin-Akt-mTOR pathway

Enhanced macrophage recruitment, promoted M2-like polarization

[31]

CL1-5

miR-103a

Hypoxia

Macrophages

PTEN and Akt/Stat3

Increased M2-type polarization, enhanced cancer progression and tumor angiogenesis

[33]

SK-LU-1

miR-125b et al

Double-targeted (wild-type p53 and microRNA-125b) transfection

J774 macrophages

/

J774 macrophages repolarized towards M1 phenotype

[34]

A549/LLC

/

/

DCs

PD-L1

Reduced the expression of PD-L1 of DCs, down-regulated the population of Tregs

[37]

A549

/

Rab27a

DCs, CD4⁺ T-cell

/

Induced higher levels of cytokines (IL-1β, TNF-α, RANTES), promoted CD4⁺ T-cell proliferation

[40]

IGR-Heu

TGF-β, miR-23a

Hypoxia

NK

NKG2D

Decreased the cell surface expression of the activating receptor NKG2D, thereby inhibiting NK cell function

[44]

LLC

miR-21、miR-29a

/

TAM

TLR8

Activated NF-κB and promoted the secretion of inflammatory cytokines TNF-α and IL-6

[27]

NK

DNAM1

IL-2/IL-15

Lung tumor cell

DNAM1-ligands

Involved in NK mediated cytotoxicity and result in killing of tumor cells

[47]

LLC

PD-L1

/

DC

/

Blocked the differentiation of DCs and increased the rates of Treg

[49]

Treg

let-7d

Rab27a and Rab27b

Th1

Cox-2

Suppressed Th1 cell proliferation and cytokine secretion

[53]

Lung cancer cell

EGFR

/

DCs

/

Induced tolerogenic DCs, which effected on Th0 to produce Treg

[54]

KRAS mutant NSCLC

KRAS protein

K-ras gene mutant

CD4⁺ T-cell

IFN signaling

Induced CD4⁺ T phenotypic conversion to FOXP3⁺ Treg-like cells that are immune-suppressive

[56]

CAFs

SNAL1

/

Lung tumor cell

E-ca, a-SMA, vimentin

Induced metastasis and drug resistance in NSCLC

[13]

Mesenchymal lung cancer cell

ZEB1 mRNA

/

Bronchial epithelial cell

/

Transferred chemoresistance and mesenchymal phenotypes to bronchial epithelial cell via ZEB1 mRNA

[63]

BMSCs

miR-193a-3p, miR-210-3p and miR-5100

Hypoxia

Epithelial and mesenchymal cell

STAT3 signal

Promoted cancer cell invasion and EMT

[15]

A549/SPC-A-1-BM

miR-499a-5p

/

Epithelial and mesenchymal cell

mTOR signal

Enhanced cell proliferation, migration and EMT via mTOR pathway

[64]

CL1-5 cells

miR-23a

Hypoxia

Endothelial cells

PHD 1 and 2

Promoted angiogenesis and tumour growth

[76]

CL1-5 cells

miR-23a

Hypoxia

Endothelial cells

ZO-1

Increased vascular permeability and cancer trans-endothelial migration

[76]

A549

ANGPTL4

γ-ray irradiated or hypoxic conditions

Human umbilical vein endothelial cells

/

Contributed to the migration of NSCLC as well as the angiogenesis of HUVECs

[77]

Lung cancer cell

miR-210

/

CAFs

TET2 and JAK2/STAT3

Promoted release of proangiogenic factors VEGF, MMP9 and FGF2

[68]

Cigarette smoke extract (CSE)-transformed human bronchial epithelial (HBE) cells

miR-21

STAT3

(Human bronchial epithelial)HBE, human umbilical vein endothelial cells (HUVEC)

STAT3

Lead to STAT3 activation, which increases VEGF levels in recipient cells

[79]

hek293t

miR-497

/

A549, HUVECs

VEGF-A, HDGF, CCNE1

Contributed to tumor growth and angiogenesis

[80]

LLC2

miR-126-3p, miR-27b, miR-320, and miR-342-3p

/

/

MDSCs

Activated their immunosuppressive functions

[60]

Lung cancer cell

miR-9

/

HUVECs

SOCS5/JAK-STAT pathway

Regulated SOCS5-JAK-STAT pathway and promoted endothelial cell migration and tumour angiogenesis

[65]

A549

miR-210

TIMP-1

HUVECs

/

Downstreamed targets of miR-210: FGFRL1, E2F3, VMP-1, RAD52 and SDHD

[78]

CAFs

miR-210

/

NSCLC

UPF1

Promoted EMT by activating PTEN/PI3K/AKT pathway

[87]

H1437 and H2073

miR-142-3p

/

Endothelial and fibroblast cells

TGFβ signaling

Promoted angiogenesis through inhibition of TGF-βR1

[66]

A549

EGFR

/

Endothelial cells

MAPK and Akt pathways

Induced and modulated tumor angiogenesis

[120]

PC14HM

/

/

HBECs

/

Induced vimentin expression and EMT in HBECs

[121]

Human brain microvascular endothelial cells

S100A16 protein

/

SCLC

Δψm, prohibitin (PHB)-1

Facilitated the survival of SCLC cells through modulating the mitochondrial function

[16]

A549

lnc‐MMP2‐2

TGF‐β

Vascular endothelial cell

/

Increased vascular permeability

[84]

LLC

Exosomal RNAs

/

Lung epithelial cells

TLR3

Provided potential targets to control cancer metastasis

[81]

LLC

LRG1

A549

NSCLC, vein endothelial cells

TGF-β signaling

Promoted angiogenesis

[86]

B cell

CD39 and CD73

Hypoxia-inducible factor-1α

CD8⁺ T cell

/

Impaired CD8⁺ T cell responses

[20]

H1792 and HCC44

VEGF

TTF-1

endothelial cell

GM-CSF/VEGF axis

Contributed to angiogenesis

[85]