Table 2.
LILRB expression and function in human malignancies.
| Cancer types | LILRBs | Expression* | Clinical features | Survival (Prognosis) | Cellular roles | References |
|---|---|---|---|---|---|---|
| Hematological malignancies | ||||||
| AML | LILRB1 | Upregulated | OS (Poor) | 210 | ||
| LILRB2 | Upregulated | OS (Poor) | Support HSC expansion | 72, 210, 211, 212, 293 | ||
| LILRB3 | Upregulated | OS (Poor) | Enhance tumor cell survival, inhibit T cell activity | 198, 210, 212, 233 | ||
| LILRB4 | Upregulated | OS (Poor) | Support tumor cell infiltration and suppress T cell activity | 22, 210, 212 | ||
| LILRB5 | NS | OS (Favorable) | 97, 212 | |||
| CMML | LILRB4 | Upregulated | 213 | |||
| MM | LILRB1 | (a) Downregulated; (b) Upregulated |
Cytogenetic abnormality t(4;14) translocation | OS (Poor) | Increase susceptibility to T/NK-mediated killing; Regulate cholesterol metabolism and protect tumor cells from ferroptosis |
214, 297 |
| LILRB2 | Downregulated | 214 | ||||
| LILRB3 | Downregulated | 214 | ||||
| LILRB4 | (a) NS; (b) Upregulated |
Bone damage | OS (Poor) | Support tumor cell proliferation; Promote osteolytic lesions |
116, 214, 215, 232, 299 | |
| LILRB5 | NS | 214 | ||||
| CLL | LILRB1 | Downregulated | 216 | |||
| LILRB2 | 54.5% expression | 300 | ||||
| LILRB4 | 48.9% expression | Lymphoid tissue involvement | Regulate tumor progression | 300, 301 | ||
| ALL | LILRB2 | Downregulated | 302 | |||
| KMT2A-rearranged ALL | LILRB4 | Upregulated | 217 | |||
| ATL | LILRB4 | Inhibit tumor cell growth | 89 | |||
| CTCL | LILRB1 | 100% expression | Inhibit tumor cell proliferation | 303, 304, 305 | ||
| cHL | LILRB2 | Upregulated | OS (Poor) | 309 | ||
| Digestive system | ||||||
| EC | LILRB1 | Upregulated | 221 | |||
| LILRB2 | Upregulated | Tumor stage | 312 | |||
| HCC | LILRB1 | Downregulated | TILs | RFS/PFS (Favorable) | 313 | |
| LILRB2 | (a) Upregulated;(b) Downregulated | Gender, tumor size, cell differentiation, TILs | (a) OS (Poor); (b) OS/RFS/PFS/DFS (Favorable) |
Promote macrophage polarization to M2 phenotype and recruit immunosuppressive T cells | 196, 313, 314 | |
| LILRB3 | Downregulated | TILs | RFS/PFS (Favorable) | 313 | ||
| LILRB4 | Upregulated | TILs | RFS/PFS (Favorable) | 313 | ||
| LILRB5 | Downregulated | TILs | OS/RFS/PFS/DFS (Favorable) | 313 | ||
| GC | LILRB1 | Upregulated | Pathological stage, cell differentiation, tumor size | OS (Poor) | Inhibit the anti-tumor effect of NK cells | 205, 219, 220 |
| LILRB2 | Upregulated | 317 | ||||
| LILRB4 | Upregulated | 220 | ||||
| PDAC | LILRB1 | Upregulated; Downregulated |
Pathological stage | OS (Poor) | 219, 321 | |
| LILRB2 | Upregulated; Downregulated |
Sustain EMT and the early metastatic behavior of tumor cells | 319, 321 | |||
| LILRB3 | Downregulated | 321 | ||||
| LILRB4 | Downregulated | OS/RFS (Favorable) | 321 | |||
| CRC | LILRB1 | Upregulated | OS (Poor) | 219 | ||
| LILRB2 | Upregulated | Gender, cell differentiation, vascular involvement, LN metastasis, tumor stage | OS (Poor) | Regulate tumor cell proliferation, invasion, migration, and angiogenesis | 218, 231, 322, 323 | |
| LILRB3 | Upregulated | LN metastasis, tumor stage | OS/PFS (Poor) | Inhibit T-cell infiltration and promote M2-like TAM accumulation | 324 | |
| LILRB4 | Upregulated | LN metastasis, tumor stage, CD45RO+ T cell count | OS (Poor) | 325 | ||
| Respiratory system | ||||||
| NSCLC | LILRB1 | 51.5% expression | Tumor stage | 107 | ||
| LILRB2 | Upregulated | Cell differentiation, LN metastasis, tumor stage, age, TILs | OS/PFS (Poor) | Promote tumor growth, invasion, migration, and angiogenesis; Recruit M2-like TAMs and impair T cell response; Enhance resistance to radiation |
197, 199, 222, 223, 224, 327, 328, 329 | |
| LILRB4 | Upregulated | Cell differentiation, tumor size, vascular involvement, tumor stage | OS (Poor) | Enhance tumor cell migration, invasion, and angiogenesis | 230 | |
| Reproductive system | ||||||
| BC | LILRB1 | Upregulated | Pathological stage | OS (Poor) | 219 | |
| LILRB2 | Upregulated | TILs, LN metastasis | OS/PFS (Poor) | Promote immune evasion; Promote tumor growth, and induce effector T cell senescence; Reprogram toward aerobic glycolysis |
195, 229, 336, 337 | |
| OC | LILRB1 | Upregulated | Age, tumor stage | 225 | ||
| Endometrial cancer | LILRB2 | Upregulated | OS (Poor) | Support tumor cell expansion and migration | 228 | |
| Urinary system | ||||||
| ccRCC | LILRB1 | 60% expression | 227 | |||
| LILRB2 | 60% expression | 227 | ||||
| LILRB3 | Upregulated | OS (Poor) | 344 | |||
| Nervous system | ||||||
| Glioma | LILRB1 | Upregulated | Tumor size | OS (Poor) | Enhance tumor cell proliferation, migration and invasion | 118 |
| Glioblastoma | LILRB1 | Upregulated | 349 | |||
| LILRB2 | Upregulated | Pathological stage | OS/DFS (Poor) | Induce MDSC formation and expansion | 349, 350 | |
| LILRB3 | Upregulated | 349 | ||||
| LILRB4 | Upregulated | 349 | ||||
| Cutaneous tumors | ||||||
| Melanoma | LILRB2 | Upregulated | Promote tumor growth; Induce effector T cell senescence |
229 | ||
| Tumors of other system | ||||||
| OSCC | LILRB1 | Downregulated | 352 | |||
| TC | LILRB1 | Upregulated | Pathological stage | OS (Poor) | 219 |
ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; ATL, acute T cell leukemia; BC, breast cancer; ccRCC, clear cell renal cell carcinoma; cHL, classical Hodgkin lymphoma; CLL, chronic lymphocytic leukemia; CMML, chronic myelomonocytic leukemia; CRC, colorectal cancer; CTCL, cutaneous T-cell lymphoma; DFS, disease-free survival; EC, esophageal carcinoma; EMT, epithelial-mesenchymal transition; GC, gastric cancer; HCC, hepatocellular carcinoma; HSC, hematopoietic stem cell; LN, lymph node; MDS, myelodysplastic syndrome; MDSC, myeloid-derived suppressor cell; MM, multiple myeloma; NS, no significance; NSCLC, non-small cell lung cancer; OC, ovarian cancer; OS, overall survival; OSCC, oral squamous cell carcinoma; PDAC, pancreatic ductal adenocarcinoma; PFS, progression-free survival; RFS, recurrence-free survival; TAMs, tumor-associated macrophages; TC, thyroid cancer; TILs, tumor-infiltrating lymphocytes; VEGF-C, vascular endothelial growth factor C.
*Compare the expression levels of LILRBs between tumor cells and normal cells.