Table 1 LncRNAs involved in TIME

LINK-A

—

TNBC

Upregulated in tumor cells

—

PtdIns(3,4,5)P3, GPCR, PKA, TRIM7

LINK-A-dependent downregulation of antigenicity and intrinsic tumor suppression by mediating the crosstalk between PtdIns(3,4,5)P3 and GPCR

Overall survival

[12]

LINC00665

—

HGSOC

Upregulated in tumor cells

—

FTX

Influencing the infiltration level of macrophages and DCs, and inhibiting Tregs and prevent T-cell exhaustion by FTX

Overall survival

[10]

GNAS-AS1

Macrophages

ER+ Breast cancer

Upregulated in tumor cells and M2 macrophages

miR-433-3p

GATA3

Accelerating M2 macrophage polarization

—

[30]

GNAS-AS1

Macrophages

Non-small cell lung cancer

Upregulated in tumor cells and M2 macrophages

miR-4319

NECAB3

Regulating macrophage polarization

Overall survival, metastasis-free survival

[31]

CCAT1

Macrophages

Prostate cancer

Downregulated in M2 macrophages

miR-148a

PKCζ

Regulating macrophage polarization

—

[32]

NIFK-AS1

Macrophages

Endometrial Cancer

Downregulated in M2 macrophages

miR-146a

Notch1

Inhibiting M2 macrophage polarization

—

[36]

XIST

Macrophages

Lung cancer

Upregulated in M2 macrophages

—

—

Regulating macrophage polarization

—

[37]

MM2P

Macrophages

—

Upregulated in M2 macrophages

—

STAT6

Accelerating M2 macrophage polarization

—

[38]

ANCR

Macrophages

Gastric cancer

Upregulated in tumor cells

—

FoxO1

Promoting tumor metastasis through hindering M1 type differentiation of macrophages by facilitating FoxO1 ubiquitination degradation

—

[39]

LincRNA-p21

Macrophages

Breast cancer

Upregulated in M2 macrophages

—

MDM2, P53, NF-κB, STAT3

Inhibiting macrophage polarization into pro-inflammatory M1 by promoting its interaction with p53

—

[40]

LncRNA-cox-2

Macrophages

HCC

Downregulated in M2 macrophages

—

—

Preventing immune evasion and metastasis of cancer by altering M1/M2 macrophage polarization

—

[41]

MALAT1

Macrophages

Thyroid cancer

Upregulated in tumor cells and M2 macrophages

—

FGF2

MALAT1-mediated FGF2 protein secretion from TAMs inhibits inflammatory cytokines release, promotes proliferation, migration, and invasion of tumor cells and induces vasculature formation

—

[42]

SBF2-AS1

Macrophages

Pancreatic cancer

Upregulated in M2 macrophages

miR-122-5p

XIAP

M2 macrophages secrete SBF2-AS1-rich exosomes to promote tumor progression.

—

[43]

LINC00662

Macrophages

HCC

Upregulated in tumor cells

miR-15a, miR-16, miR-107

WNT3A, Wnt/β-catenin signaling

Increasing tumor-derived WNT3A and activating Wnt/β-catenin signaling in macrophages via paracrine manner, and promoting M2 macrophages polarization

Overall survival, differentiation, tumor size, microvascular invasion

[45]

MALAT1

Macrophages

HCC

Upregulated in tumor cells

miR-140

VEGF-A

Regulating macrophage polarization

—

[46]

RPPH1

Macrophages

Colorectal cancer

Upregulated in tumor cells

—

TUBB3

Inhibiting TUBB3 ubiquitination and enhancing exosomes-mediated macrophages M2 polarization and influences the tumor microenvironment

Overall survival, TNM stages

[47]

BCRT1

Macrophages

Breast cancer

Upregulated in tumor cells and M2 [45]macrophages

miR-1303

PTBP3

Promoting M2 polarization of macrophages, mediated by exosomes, and accelerating cancer progression

Overall survival

[48]

TUC339

Macrophages

HCC

Upregulated in HCC-derived exosomes

—

—

Regulating macrophage activation and polarization

—

[49]

CASC2c

Macrophages

Glioblastoma

Downregulated in tumor cells

miR-338-3p

FX

Inhibiting macrophage migration and polarization to the M2 subtype by FX

—

[50]

CamK-A

Macrophages

Breast cancer

Upregulated in tumor cells

—

PNCK, IκBα, NF-κB, VEGF, IL-8, and GLUT3

Promoting infiltrated macrophage recruiting, angiogenesis, tumor microenvironment remodeling, and cancer development,

 Overall survival, recurrence-free survival 

[51]

Lnc-C/EBPβ

MDSCs

—

Upregulated in MDSCs

—

C/EBPβ isoform LIP

 Controlling immunosuppressive function and differentiation of MDSCs by a set of target transcripts

—

[52]

Lnc-C/EBPβ

MDSCs

—

Upregulated

—

IL4il, C/EBPβ isoform LIP, WDR5

Promoting PMN-MDSCs but impede differentiation of M-MDSCs

—

[53]

RNCR3

MDSCs

—

Upregulated in MDSCs

miR-185-5p

Chop

Regulating MDSC differentiation and suppressive function to influence tumor growth by RNCR3/miR-185-5p/Chop axis

—

[54]

Lnc-chop

MDSCs

—

Upregulated in MDSCs

—

CHOP, C/EBPβ isoform LIP

Interacting with CHOP and the C/EBPβ isoform LIP to regulate immunosuppressive function of MDSCs

—

[55]

Olfr29-ps1

MDSCs

—

Upregulated

miR-214-3p

MyD88

 Regulating the differentiation and function of M-MDSCs by a m6A-modified Olfr29-ps1/miR-214-3p/MyD88 regulatory network

—

[56]

Pvt1

MDSCs

—

Upregulated

—

C-myc

Regulating the immunosuppression activity of PMN-MDSCs by c-myc

—

[57]

AK036396

MDSCs

—

Upregulated

—

Ficolin B

Inhibiting maturation and accelerating immunosuppression of PMN-MDSCs by Enhancing the Stability of Ficolin B

—

[58]

MALAT1

MDSCs

Lung Cancer

Downregulated 

—

—

Negatively regulating the generation of MDSCs

—

[59]

RUNXOR

MDSCs

Lung cancer

Upregulated

—

RUNX1 

Mediating MDSCs associated immunosuppression by targeting RUNX1

Smoking history, TNM stage, histological tumor type and lymph node metastasis

[60]

HOTAIRM1

MDSCs

Lung Cancer

Downregulated 

—

HOXA1

 Regulating MDSCs associated immunosuppression by targeting HOXA1

Smoking history, TNM stage, histological tumor type and lymph node metastasis

[61]

HOTAIR

MDSCs

HCC

Upregulated

—

CCL2

Promoting proliferation of macrophages and MDSCs 

—

[62]

Gm43181

Neutrophils

—

Upregulated in neutrophils

—

CXCR2

Provoking inflammation by regulating the recruitment and activation of neutrophils into the specific tissues

—

[63]

MALAT1

Neutrophils

—

Upregulated

—

p300, IL-8

Ameliorating the inflammatory injury by inhibiting chemotaxis of neutrophils through p300-mediated downregulation of IL-8

—

 [64]

XIST

Neutrophils

—

Upregulated

miR-21

IL-12A

Increasing IL-12A by binding to miR-21, thereby inducing neutrophil extracellular trap formation 

—

[65]

TCL6

Neutrophils

Breast cancer

Downregulated in tumor cells

—

—

—

Overall survival

[11]

HOTTIP

Neutrophils

Ovarian cancer

Upregulated in tumor cells

—

c-jun, IL-6, PD-L1

Enhancing IL-6 expression to potentiate immune escape of tumor cells by upregulating the expression of PD-L1 in neutrophils

Overall survival

[66]

Lnc-DC

DCs

—

Upregulated in DCs

—

 STAT3, TLR9, TIMP, MMP

Regulating the differentiation and capacity of DCs by activating the transcription factor STAT3

—

[67,68,69,70]

NEAT1

DCs

—

Upregulated in DCs

miR-3076-3p

NLRP3

Inducing tolerogenic phenotype in DCs by inhibiting activation of NLRP3 inflammasome

—

[71]

HOTAIRM1 

DCs

—

Downregulated in DCs

miR-3960

HOXA1

Regulating DC differentiation by competitively binding to endogenous miR-3960

—

[72]

Lnc-Dpf3

DCs

—

Upregulated in DCs

—

HIF-1α

CCR7-inducible lnc-Dpf3 restrains DC migration by inhibiting HIF-1α-mediated glycolysis

—

[73]

MALAT-1

DCs

Colon cancer

Upregulated in DCs

—

Snail

Blocking MALAT-1 significantly decreases the TADC-conditioned medium and CCL5-mediated migration and invasion by decreasing the Snail

—

[74]

SNHG16

B cells

DLBCL

Upregulated in tumor cells

miR-497-5p

PIM1

Promoting proliferation and inhibits apoptosis of lymphoma cells by targeting miR-497-5p/PIM1 axis

—

[75]

TUG1

B cells

DLBCL

Upregulated in tumor cells

—

MET 

Regulating tumor growth by ubiquitination of MET

—

[76]

SNHG14

B cells

DLBCL

Upregulated in tumor cells

miR-5590-3p

ZEB1

SNHG14/miR-5590-3p/ZEB1 positive feedback loop promotes lymphoma progression and immune evasion by PD-1/PD-L1 checkpoint

—

[77]

MALAT1

B cells

DLBCL

Upregulated in tumor cells

miR-195

PD-L1

Promoting tumorigenesis and immune escape of lymphoma by sponging miR-195

—

[78]

MINCR

B cells

BL

Upregulated in tumor cells

—

AURKA, AURKB, and CDT1

Controlling cell cycle by participating in MYC transcriptional network

—

[79]

NEAT1

B cells

DLBCL

Upregulated in tumor cells

miR-34b-5p

GLI1

Promoting B cell proliferation and lymphomagenesis by the miR-34b-5p-GLI1 pathway.

—

[80]

FIRRE

B cells

DLBCL

Upregulated in tumor cells

—

Wnt/β-catenin pathway

Promoting the development of lymphoma by Wnt/β-catenin signaling pathway

Overall survival

[81]

PANDA

B cells

DLBCL

Downregulated in tumor cells

—

MAPK/ERK pathway

Inhibiting the growth of lymphoma by inactivation of MAPK/ERK signaling pathway

Overall survival, recurrence-free survival, B symptoms, Ann arbor stages, CHOP-like treatment, Rituximab and IPI

[82]

OR3A4

B cells

DLBCL

Upregulated in tumor cells

—

 Wnt/β-catenin signaling

Promoting cell proliferation through activating Wnt/β-catenin signaling pathway

Overall survival

[83]

SMAD5-AS1

B cells

DLBCL

Downregulated in tumor cells

miR-135b-5p

APC, Wnt/β-catenin pathway

Inhibiting proliferation of lymphoma through Wnt/β-catenin pathway via targeting miR-135b-5p to elevate expression of APC

—

[84]

HULC

B cells

DLBCL

Upregulated in tumor cells

—

Bcl-2, cyclin D1

Regulating cell proliferation and inducing apoptosis by Bcl-2 and cyclin D1

Overall survival, progression–free survival, Ann Arbor stages, B symptoms, CHOP-like treatment, Rituximab and IPI

[85]

HOTAIR

B cells

DLBCL

Upregulated in tumor cells

—

PI3K/AKT/NF-κB pathway

Promoting cell proliferation by PI3K/AKT/NF-κB pathway

Overall survival, tumor size, clinical stage, B symptoms and IPI

[86]

LUNAR1

B cells

DLBCL

Upregulated in tumor cells

—

E2F1, cyclin D1 and p21

Regulating cell proliferation by E2F1, cyclin D1 and p21

Overall survival, progression-free survival, stage, rituximab and IPI

[87]

PEG10

B cells

DLBCL

Upregulated in tumor cells

—

—

—

Overall survival, B symptoms, CHOP-like treatment, Rituximab and IPI

[88]

MALAT-1

B cells

DLBCL

Upregulated in tumor cells

—

LC3-II/LC3-I, p62, ATG5

 Regulating autophagy-related signaling pathway on chemotherapy resistance

—

[89]

FAS-AS1

B cells

Non-Hodgkin's lymphomas

Upregulated in tumor cells

—

RBM5

Regulating of the sFas expression by interacting with RBM5 to influence cell apoptosis

—

[90]

FENDRR

Tregs

HCC

Downregulated in Tregs

miR-423-5p

GADD45B

 Inhibiting the Treg-mediated immune escape of tumor cells through upregulating GADD45B by sponging miR-423-5p

—

[91]

SNHG1

Tregs

Breast cancer

Upregulated in Tregs

miR-448

IDO

Accelerating the differentiation of Treg cells and promoting the immune escape of cancer by regulating miR-448/IDO axis

—

[92]

POU3F3

Tregs

Gastric cancer

Upregulated in Tregs

—

TGF-β/SMAD2/3 pathway

Promote the distribution of Tregs in peripheral blood T cell, increasing cell proliferation by recruiting TGF-β as well as activating TGF-β signal pathway

Tumor size

[93]

lnc-EGFR

Tregs

HCC

Upregulated in Tregs

—

EGFR, AP-1/NF-AT1 axis

Stimulating Treg differentiation, suppresses CTL activity and promoting HCC growth in an EGFR-dependent manner.

 Tumor size

[94]

RP11-323N12.5

Tregs

Gastric cancer

Upregulated in tumor cells

—

YAP1, TAZ, TEAD, Hippo signaling

Promoting Treg cell differentiation by enhancing YAP1 transcription in T cells

Disease-free survival, stage

[95]

SNHG16

Tregs

Breast cancer

Upregulated in tumor cells

miR-16-5p

SMAD5 

Breast cancer-derived exosomes transmit SNHG16 to induce CD73+γδ1 Treg cells by activation of the TGF-β1/SMAD5 pathway

—

[96]

Lnc-sox5

CTLs

Colorectal cancer

Upregulated in tumor cells

—

IDO1

Regulating the infiltration and cytotoxicity of CD3+CD8+T cells by IDO1, and unbalancing the TME

Metastasis

[97]

NEAT1

CTLs

Lung cancer

Upregulated in tumor cells

—

DNMT1, P53, cGAS/STING

Interacting with DNMT1 to regulate malignant phenotype of cancer cell and cytotoxic T cell infiltration by epigenetic inhibition of p53, cGAS, and STING

 Tumor stage, lymph node metastasis.

[98]

NEAT1

CTLs

HCC

Upregulated in CTLs

miR-155

Tim-3

Regulating the antitumor activity of CD8+ T cells against HCC by miR-155/Tim-3 axis

—

[99]

 Lnc-Tim3

CTLs

HCC

Upregulated in CTLs

—

Tim-3, Bat3, Lck/ NFAT1/AP-1 pathway

Exacerbating CD8+ T cell exhaustion by binding to Tim-3 and inducing nuclear translocation of Bat3

—

[100]

LINC00473

CTLs

Pancreatic cancer

Upregulated in tumor cells

miR-195-5p

PD-L1

Inhibiting activation of CD8+ T cells by sponging miR‐195‐5p to elevate the expression of PD‐L1

—

[101]

SNHG14

CTLs

DLBCL

Upregulated in tumor cells

miR-5590-3p

ZEB1, PD-1

Promoting apoptosis of CD8+ T cells by PD-1/PD-L1 immune checkpoint, and eventually leading to the immune evasion

—

[77]

MALAT1

CTLs

DLBCL

Upregulated in tumor cells

miR-195

PD-L1

Promoting apoptosis of CD8+ T cells and immune escape of lymphoma

—

[78]

GM16343

CTLs

—

Upregulated in CTLs

—

IFN-γ

Promoting IL-36β to regulate the TME by CD8+ T cells

Overall survival

[102]

NKILA

CTLs

breast and lung cancer 

Upregulated in CTLs

—

NF-κB

Regulating T cell sensitivity to AICD by inhibiting NF-κB activity

Overall survival

[103]

INCR1

CTLs

—

Upregulated in CTLs

—

PD-L1, JAK2, STAT1, and IDO1, HNRNPH1

Regulating tumor IFNγ signaling and CTL-mediated killing

—

[104]

Lnc-CD56

NK cells

—

Upregulated in NK cells

—

CD56

Serving as a positive regulator of CD56 in primary human NK cells and differentiated NK cells from human CD34+ hematopoietic progenitor cells. 

—

[105]

IFNG-AS1

NK cells

—

Upregulated in NK cells

—

IFNG

Triggering of the natural cytotoxicity receptors induces lncRNA IFNG-AS1 expression, and IFNG-AS1 increases IFN-γ secretion

—

[106]

GAS5

NK cells

Gastric cancer

Downregulated in NK cells

miR-18a

—

Promoting NK cell cytotoxicity against gastric cancer by regulating miR-18a

—

[107]

GAS5

NK cells

HCC

Downregulated in NK cells

miR-544

RUNX3

Enhancing the killing effect of NK cell on liver cancer by regulating miR-544/RUNX3

—

[108]

linc-EPHA6-1

NK cells

Lung cancer

—

miR-4485-5p

NKp46 

IFNβ-induced exosomal linc-EPHA6-1 promotes cytotoxicity of NK cells by miR-4485-5p to increase NKp46 expression

—

[109]