Table 4.
Tumor cell-expressed lncRNAs that modulate TIL populations.
| LncRNA | LncRNA type | Molecular Interaction | Cancer type | T cell subset | Species | Affected Signaling Molecules/Pathway | Function | Ref. |
|---|---|---|---|---|---|---|---|---|
| SNHG20 | intergenic | – | ESCC | T cells | h | ATM/JAK/PD-L1 | LncRNA SNHG20 regulates p-ATM, pJAK1/2 and PD-L1 expression and drives metastasis and ESCC progression. | (148) |
| Malat1 | intergenic | lncRNA- RNA | DLBCL | CD8+ T cells | h, m | miR-195/PD-L1 | LncRNA Malat1 induces tumor growth and immune evasion in DLBCL by sponging miR-195 to regulate PD-L1 expression. | (149) |
| INCR1 | antisense | lncRNA- protein | GBM, BC, NSCLC, melanoma |
CD8+ T cells | h | HNRNPH1/PD- L1/JAK2/IFN-γ signaling |
IFN-γ-stimulated lncRNA INCR1 binds HNRNPH1 to promote PD-L1 and JAK2 expression. Silencing INCR1 sensitizes tumor cells to T cell-mediated killing. | (89) |
| LIMIT | antisense | lncRNA- DNA | Melanoma | CD8+ T cells | h, m | GBP/HSF1/MHC | IFN-γ-induced LIMIT stimulates the GBP cluster, activates HSF1 and thereby increases MHC-I but not PD-L1. LIMIT correlated with MHC-I and ICI therapy response in patients. | (150) |
| EPIC1 | intergenic | lncRNA- protein | 32 cancer types | CD8+ T cells | h | EZH2/IFNγ-JAK- STAT1 signaling |
EPIC1 blocks IFNγ-JAK-STAT1 signaling via epigenetic silencing of IFNGR1, which decreases MHC-I expression and CTL infiltration into tumors. | (92) |
| LINK-A | Intergenic | lncRNA- protein | TNBC | CD8+ T cells | h, m | LINK-A/ PKA/TRIM71 | LINK-A (LINC01139) acts as an oncogene by downregulating cancer cell antigen presentation via suppression of PKA-mediated phosphorylation of the E3 ubiquitin ligase TRIM71. | (151) |
| NEAT1 | intergenic | lncRNA- protein | LC | CD8+ T cells | h, m | DNMT1/cGAS- STING/P53 | LncRNA NEAT1 promotes lung cancer growth and decreases tumor-infiltrating T cells by interacting with DNMT1 thereby inhibiting the expression of cGAS/STING and P53. | (152) |
| SOX2-OT | intergenic | lncRNA- RNA | NSCLC | CD8+ T cells | h | miR-30d-5p/ PDK1/mTOR/PD-L1 | SOX2-OT upregulates PDK1 expression by sponging miR- 30d-5p and drives PD-L1 through mTOR signaling. | (153) |
| KCNQ1OT1 | antisense | – | CRC | CD8+ T cells | h | CD155 | KCNQ1OT1 is a prognostic biomarker, modulates CD155 expression, thereby induces CD8+ T cell exhaustion in CRC. | (154) |
| LINC00473 | intergenic | lncRNA- RNA | PC | CD8+ T cells | h | miR-195-5p/PD-L1 | LINC00473 drives tumorigenesis by sponging miR195-5p, increases PD-L1 thus inhibiting CD8+ T cell activation. | (155) |
| SNHG14 | intergenic | lncRNA- RNA | DLBCL | CD8+ T cells | h, m | miR-5590-3p/ ZEB1/PD-L1 | SNHG14 sponges miR-5590-3p, upregulates ZEB1 and promotes SNHG14 and PD-L1 expression, thereby driving DLBCL progression and immune escape. | (156) |
| HCG18 | - | lncRNA- RNA | CRC | CD8+ T cells | m | HCG18/miR-20b-5p/ PD-L1 | LncRNA HCG18 expressed in CRC inhibits CD8+ T cells and induces resistance to cetuximab. Functionally, HCG18 enhances PD-L1 expression by sponging miR20b-5p. | (157) |
| SNHG1 | intergenic | lncRNA- RNA | RCC | CD8+ T cells | h | SNHG1/miR-129-3p/ STAT3/PD-L1 | SNHG1 targets STAT3 / PD-L1 by binding miR-129-3p. This promotes tumor immune evasion by inhibiting CD8+ T cells. | (158) |
| lnc-Sox5 | - | lncRNA- protein | CRC | CD8+ T cells, Treg cells | h | IDO1 | Lnc-Sox5 suppresses infiltration and cytotoxicity of CD8+ T cells by promoting Treg cells via IDO1. | (88) |
| LINC00301 | intergenic | lncRNA- protein lncRNA- RNA |
NSCLC | CD8+ T cells, Treg cells | h, m | FOXC1/LINC00301/ EZH2 or miR-1276/ HIF-1α |
LINC00301 modulates the TME by increasing the Treg/CD8+ T cell ratio. It either targets nuclear EZH2 or cytoplasmic miR-1276 to regulate HIF-1α. | (137) |
| NNT-AS1 | antisense | - | HCC | CD4+ T cells | h | TGF-β signaling | NNT-AS1 is a potential biomarker in HCC. It activates the TGF-β pathway and decreases tumor-infiltrating CD4+ T cells. | (159) |
| HOXA-AS2 | antisense | lncRNA- RNA | GBM | Treg cells | h | HOX-AS2/miR-302a/ KDM2a/JAG1 | LncRNA HOXA-AS2 targets miR-302a, which stimulates the KDM2A/JAG1 pathway to promote Treg cell proliferation. | (160) |
| circRNA- 002178 | circular | lncRNA- RNA | LUAD | CD8+ T cells | h | PD-L1/PD-1 | CircRNA-002178 enhances PD-L1 expression via sponging miR-34 in cancer cells to induce T cell exhaustion. CircRNA- 002178 can also be transmitted via exosomes to induce PD-1 expression in CD8+ T cells. | (161) |
| circIGF2BP3 | circular | lncRNA- RNA | NSCLC | CD8+ T cells | h | miR328-3p/miR3173- 5p/PKP3/FXR1/ OUTB1/PD-L1 |
CircIGF2BP3 blocks CD8+ T cell infiltration by sponging miR328-3p and miR3173-5, which activates the PKP3/FXR1/ OUTB1 axis to promote PD-L1 expression in NSCLC. | (162) |
| circUSP7 | circular | lncRNA- RNA | NSCLC | CD8+ T cells | h | miR-934/SHP2 | The exosomal circUSP7 promotes CD8+ T cell dysfunction and resistance to anti-PD1 therapy by sponging miR-934 and inducing SH2 expression. | (163) |
BC, breast cancer; CRC, colorectal cancer; DLBCL, diffuse large B-cell lymphoma; ESCC, esophageal squamous cell carcinoma; GBM, glioblastoma; HCC, hepatocellular carcinoma; LC, lung cancer; LUAD, lung adenocarcinoma; NSCLC, non-small cell lung cancer; PC, pancreatic cancer; RCC, renal cell carcinoma; TNBC, triple-negative breast cancer; h, human; m, mouse.