Table 1.
Summary of evidence for the role of lncRNA in the tumor immune microenvironment.
| LncRNA | Cancer type | Related immune cell | Involved Molecules or pathways | Mechanisms | Ref |
|---|---|---|---|---|---|
| lnc-CHOP | MM, LLC, BC | MDSCs | CHOP | Promotes the activation of C/EBPβ and upregulates the expression of arginase-1, NO synthase 2, NADPH oxidase 2, and cyclooxygenase-2, which are related to the immunosuppressive function of MDSCs in inflammatory and tumor environments. | (60) |
| RNCR3 | – | MDSCs | mir-185-5p | RNCR3/miR-185-5p/Chop autologously strengthening network promotes MDSC differentiation and suppressive functions in response to extracellular inflammatory and tumor-associated signals. | (61) |
| Olfr29-ps1 | MM | MDSCs | miR-214-3p | Olfr29-ps1 may regulate the differentiation and function of MDSCs through a m6A-modified Olfr29-ps1/miR-214-3p/MyD88 regulatory network. | (62) |
| Pvt1 | LLC | MDSCs | Arg1 and ROS | Enhances G-MDSC-mediated immunosuppression and inhibits the antitumor T cell response. | (63) |
| MALAT1 | LC | MDSCs | Arg1 | Negatively regulates MDSCs. | (64) |
| HOTAIRM1 | LC | MDSCs | HOXA1-miR124 | HOTAIRM1 enhances the expression of HOXA1 in MDSCs and high levels of HOXA1, the target gene of HOTAIRM1, delays tumor progression and enhances the antitumor immune response by downregulating the immunosuppression of MDSCs. | (65) |
| RUNXOR | LC | MDSCs | Arg1 | RUNXOR recruits EZH2 and RUNX1 to epigenetically regulate the RUNX1 gene in AML cells. | (66) |
| lnc-C/EBPβ | LCC, CC | MDSCs | Arg-1, CYBB (NOX2), NOS2, ptgs2(COX2) | Controls the immune-suppressive function and differentiation of MDSCs. | (67, 68) |
| lnc-EGFR | HCC | Tregs | EGFR, AP-1/NF-AT1 | Stimulates Treg differentiation, suppresses CTL activity, and promotes HCC growth in an EGFR dependent manner. | (69) |
| SNHG1 | BC | Tregs | miR-448/IDO | Accelerates the differentiation of Treg cells and promotes the immune escape of cancer by regulating the miR-448/IDO axis. | (30) |
| Flicr | – | Tregs | FoxP3 | Escape from dominant Treg control during infection or cancer, at the cost of heightened autoimmunity. | (70) |
| Flatr | – | Tregs | FoxP3 | Flatr promotes the expression of FOXP3 and enhances the immunosuppressive function of Tregs. | (71) |
| SNHG16 | BC | Tregs | miR-16-5p, TGF-β1/SMAD5 | Breast cancer-derived exosomes transmit SNHG16 to induce CD73+ γδ1 Treg cells by activating the TGF-β1/SMAD5 pathway. | (72) |
| POU3F3 | GC | Tregs | TGF-β/SMAD2/3 | Promotes the distribution of Tregs among peripheral blood T cells, increases cell proliferation by recruiting TGF-β, as well as activating the TGF-β signaling pathway. | (73) |
| RP11-323N12.5 | GC | Tregs | YAP/TAZ/TEAD Hippo signaling | Promotes Treg cell differentiation by enhancing YAP1 transcription in T cells. | (74) |
| FENDRR | HCC | Tregs | miR-423-5p/GADD45B | Inhibits Treg-mediated immune escape of tumor cells through upregulating GADD45B by sponging miR-423-5p. | (75) |
| GNAS-AS1 | NSCLC, BC | Macrophage | miR-4319, miR-433-3p, p53 | Promotes M2 polarization of macrophages and NSCLC cell progression via directly inhibiting miR-4319. GNAS-AS1/miR-433-3p/GATA3 axis promotes the proliferation and metastasis of ER+ breast cancer cells by accelerating M2 macrophage polarization. |
(76, 77) |
| XIST | LC | Macrophage | TCF-4 | TCF-4 regulates lncRNA XIST in M2 polarization and provides novel insight into TAM regulation. | (78) |
| NIFK-AS1N | EC | Macrophage | NIFK-AS1/miR-146a/NOTCH1 axis | NIFK-AS1 inhibits the M2-like polarization of macrophages via targeting miR-146a, thereby reducing the estrogen-induced proliferation, migration, and invasion of endometrial cancer cells. | (79) |
| COX-2 | HCC | Macrophage | IL-12, iNOS, and TFN-alpha (M1), Arg1, IL-10, and Fizz-1(M2) | Inhibits HCC immune evasion and tumor growth by inhibiting the polarization of M2 macrophages. | (80) |
| SBF2-AS1 | PC | Macrophage | miR-122-5p/XIAP | lncRNA SBF2-AS1 in M2 macrophage-derived exosomes increases miR-122-5p expression to restrain XIAP expression, which further inhibits PC progression. | (81) |
| CCAT1 | PC | Macrophage | miR-148a/PKCζ axis | Inhibits M2 polarization by down-regulating miR-148a. | (82) |
| Lnc-P21 | BC | Macrophage | miR-1303 | Promotes M2 Polarization in the tumor microenvironment, which might be caused by MDM2 eliciting proteasome-dependent p53. TAMs with an lincRNA-p21 knockdown induced cancer cell apoptosis, and inhibited tumor cell migration and invasion. | (83) |
| BCRT1 | BC | Macrophage | miR-433-3p sponging, IL-10 and Arg1 | LncRNA BCRT1 competitively binds with miR-1303 to prevent the degradation of its target gene PTBP3, which acts as a tumor-promoter in breast cancer. LncRNA BCRT1 overexpression could promote M2 polarization of macrophages, mediated by exosomes. | (84) |
| LINC00662 | HCC | Macrophage | Wnt/β-catenin | LINC00662 activates Wnt/β-catenin signaling in macrophages in a paracrine manner and further promotes M2 macrophage polarization. | (85) |
| MALAT1 | HCC | Macrophage | miR-140, VEGF-A | MALAT1-mediated FGF2 protein secretion from TAMs inhibits inflammatory cytokine release, promotes proliferation, migration, and invasion; the interaction between MALAT1 and miR-140 regulates angiogenesis and immunosuppressive properties. | (86, 87) |
| TUC339 | HCC | Macrophage | IL-1 β, TNFα | TUC339 in macrophages diminishes the expression of M(IL-4) markers upon IL-4 treatment while overexpression of TUC339 in macrophages enhances M(IL-4) markers upon IFN-γ + LPS treatment, suggesting a critical function of TUC339 in the regulation of macrophage M1/M2 polarization. | (88, 89) |
| RPPH1 | CRC | Macrophage | TUBB3 | CRC cell-derived exosomes transport RPPH1 into macrophages which mediate macrophage M2 polarization, which in turn, promotes the metastasis and proliferation of CRC cells. | (90) |
| MM2P | OS | Macrophage | STAT6 | Manipulating lncRNA-MM2P in macrophages impairs macrophage-mediated promotion of tumorigenesis, tumor growth in vivo, and tumor angiogenesis. | (91) |
| RP11-361F15.2 | OS | Macrophage | miR-30c-5p, CPEB4 | RP11-361F15.2 promotes CPEB4-mediated tumorigenesis and M2-like polarization of TAMs through miR-30c-5p in OS. RP11-361F15.2 also acts as a competitive endogenous RNA (ceRNA) against miR-30c-5p, thereby binding and activating CPEB4. | (92) |
| ANCR | GC | Macrophage | FOXO1 | LncRNA ANCR in macrophages reduces the concentration of M1 macrophage marker molecules, IL-1β and IL-6, in the supernatant and inhibited M1 polarization of macrophages. | (93) |
| XIST | LC | Macrophage | IL-4, TCF-4 | Promotes M2 polarization. | (94) |
| CASC2 | GM | Macrophage | miR-338-3P | CASC2c and miR-388-3p bind to FX and commonly inhibit its expression and secretion. CASC2c suppresses M2 macrophage polarization, and alters the GBM microenvironment. | (95) |
| SNHG20 | HCC | Macrophage | STAT6 | SNHG20 may facilitate the progression of NALFD to HCC via inducing liver KC M2 polarization via STAT6 activation. | (96) |
| LIFR-AS1 | Os | Macrophage | miR-29a/NFIA | Macrophage-derived exosomal lncRNA LIFR-AS1 can promote osteosarcoma cell proliferation, invasion, and restrain apoptosis via the miR-29a/NFIA axis. | (97) |
| Lnc-Dpf3 | – | DCs | HIF-1α | DC-specific lnc-Dpf3 deficiency increases CCR7-mediated DC migration, leading to exaggerated adaptive immune responses and inflammatory injuries. | (98) |
| Lnc-DC | – | DCs | STAT3, TLR9, TIMP, MMP | Lnc-DC promotes DC maturation and inhibits trophoblast invasion without the involvement of CD4+ T cells. Lnc-DC controls the immune response by reducing the concentration of TNF-α, IL-6, IL-12, and IFN-γ, as well as increasing the concentration of IL-1β secreted by dendritic cells. | (99, 100) |
| NEAT1 | – | DCs | miR-3076-3p/NLRP3 | NEAT1 induces a tolerogenic phenotype in DCs. | (101) |
| HOTAIRM1 | – | DCs | miR-3960/HOXA1 | Regulates DC differentiation by competitively binding to endogenous miR-3960. | (102) |
| MALAT-1 | CC | DCs | SNAIL | Blocking MALAT-1 significantly decreases the TADC-conditioned medium and CCL5-mediated migration and invasion by decreasing Snail. | (103) |
| Lnc-CD56 | – | NKs | CD56 | Positive regulator of CD56. | (104) |
| GAS5 | HCC, GC | NKs | miR-544/RUNX3, miR-18a | LncRNA GAS5 overexpression enhances the killing effect of NK cell on liver cancer through regulating miR-544/RUNX3. Promotes NK cell cytotoxicity against gastric cancer by regulating miR-18a. |
(105, 106) |
| IFNG-AS1 | – | NKs | IFNG | Enhances IFN-γ in human natural killer cells. | (107) |
| lincEPHA6-1 | LC | NKs | miR-4485-5p/NKp46 | linc-EPHA6-1 acts as a competing endogenous RNA (ceRNA) for hsa-miR-4485-5p, which subsequently up-regulates natural cytotoxicity receptor (NKp46) expression. | (108) |
| lnc- TIM-3 | HCC | CD8+ T | TIM-3 | Lnc-Tim interacts with Tim-3 to release Bat3 and induces CD8+ T cell exhaustion, promoting HCC immune evasion. | (109) |
| NEAT1 | HCC | CD8+ T | miR-155, TIM-3 | Suppression of NEAT1 restrains CD8+ T cell apoptosis and enhances the cytolysis activity against HCC via modulating the miR-155/Tim-3 pathway. | (110) |
| lnc-sox5 | CC | CD8+ T | IDO1 | Suppresses the infiltration and cytotoxicity of CD8+ T cells and promotes tumorigenesis. | (111) |
MM, melanoma; LLC, Lewis lung carcinoma; BC, breast cancer; LC, lung cancer; CC: colon cancer; HCC, hepatocellular carcinoma; GC: gastric cancer; NSCLC, non-small cell carcinoma lung cancer; EC, endometrial cancer; PC, prostate cancer; CRC, colorectal cancer; OS, osteosarcoma; GM, glioblastoma multiforme; CHOP, C/EBPβ homologous protein; Arg1, arginase-1; ROS: reactive oxygen species; EZH2, enhancer of zeste homolog 2; RUNX1, runt-related transcription factor 1; EGFR, epidermal growth factor receptor; IDO: indoleamine 2,3-dioxygenase; FoxP3, forkhead box protein 3; GADD45B, DNA-damage-inducible beta protein; TCF-4, T-cell-specific transcription factor 4; XIAP, X-linked inhibitor of apoptosis protein; PKCζ, protein kinase C zeta; VEGF: vascular endothelial growth factor; TUBB3, β-III tubulin; CPEB4, cytoplasmic polyadenylation element binding protein 4; HIF-1α, hypoxia inducible factor-1 α; STAT, signal transducer and activator of transcription; TLR9, Toll-like receptor 9; TIMP, tissue inhibitor of metalloproteinase; NLRP3, NOD-like receptor pyrin domain-containing 3; IFNG, interferon gamma; TIM-3, T cell immunoglobulin and mucin-domain containing-3.