Table 2.
NKG2DL expression in human cancer.
| Tumour | Number | MICA/B | ULBP1 | ULBP2 | ULBP3 | ULBP4 | ULBP5 | Ref. |
|---|---|---|---|---|---|---|---|---|
| Breast (all subgroups) | 677 | 50% | 90% | 99% | 100% | 26% | 90% | [173] |
| Breast (all subgroups) | 530 | 97% | [172] | |||||
| Breast (no TNBC) | 31 | 91% † | 74%† | 78% ***† | 68% † | |||
| Breast (ductal) | 5 | 40% | 60% | 80% | 60% | 60% | 40% | [167] |
| Breast | 16 | 100% | [37] | |||||
| TNBC | Not provided | 93% † | 85% † | 85% ***† | 85% † | [100] ††† | ||
| Colorectal | 462 * | 100% | >50% | >50% | >50% | >50% | >50% | [168,169] |
| Colorectal | 25 | 100% † | 57% † | 72% ***† | 92% † | [100] ††† | ||
| Colorectal | 42 | 48% | [184] | |||||
| Colorectal | 5 | 100% | 100% | 80% | 100% | 80% | 80% | [167] |
| Colorectal | 86 | 85% (predominantly cytoplasmic) | [170] | |||||
| Colorectal | 13 | 100% (cytoplasmic) | [37] | |||||
| AML | 104 | 70% ¶ | [185] | |||||
| AML | 50 | 55% | [186] | |||||
| AML | 30 | Low-level expression seen | [42] | |||||
| AML | 25 | 0% | 16% | 4% | 16% | 0% | ND | [187] |
| AML | 66 | Preferential expression on monocytic subtypes | [188] | |||||
| AML | 14 | 0% 36% 64% 36% 14% | ND | [189] | ||||
| AML/CML/CLL | 25 | 56% expressed at least one ligand | [190] | |||||
| ALL | 11 | 0% | 9% | 18% | 0% | 0% | [187] | |
| ALL | 30 | 67%¶ | [185] | |||||
| CML | 11 | 82%¶ | [185] | |||||
| CLL | 3 | 0% | 0% | 0% | 0% | 0% | [187] | |
| CLL | 60 | 85%¶ | [185] | |||||
| CLL | 51 | Elevated MICA MFI on CLL cells | [178] | |||||
| AML | 50 | 55% ¶¶ | [186] | |||||
| T-ALL | 6 | 5/6 ¶¶¶ | [191] | |||||
| GBM § | 20 | 94/82% | 93% | 84% | 89% | [104] | ||
| GBM | 18 | 88.9% | 23.5% | 0% | 0% | [192] | ||
| Paediatric brain | 125 | Increased ULBP4 in low-grade gliomas only | [193] | |||||
| Neuroblastoma | 12–22 | 0%/86% ‡ 0% 50% 0% | [194] | |||||
| CCA | 82 | 96% | 100% | 77% *** | [195] | |||
| CCA | 5 | 40% | 80% | 60% | 60% | 0% | 20% | [167] |
| Bile duct | 5 | 20% | 40% | 40% | 60% | 40% | 40% | [167] |
| Ovarian | 82 | 80% | 83% | [176] | ||||
| Ovarian | 357 | 88% | 63% | 60% | 59% | 68% | 85% | [175] |
| Ovarian (HGSOC **) | 79 | 65% | 65% | 71% *** | 60% | [196] | ||
| Ovarian | 18 | 72% (cytoplasmic) | [37] | |||||
| Cervical | 5 | 20% | 20% | 40% | 100% | 80% | 40% | [167] |
| Cervical | 200 | 57% §§ | 42% §§ | 49% §§ | 56% §§ | 32% §§ | 43% §§ | [180] |
| Endometrial | 5 | 20% | 60% | 100% | 100% | 80% | 10% | [167] |
| Melanoma | 40/20 §§§ | 78/65% §§§§ | [183] | |||||
| Melanoma (metastases) | 16 | 75% | 50% | [177] | ||||
| Bladder | 23 | 91% † | 39% † | 87% ***† | 78% † | [100] ††† | ||
| NSCLC | 91 | 31% | 48% | 50% †† | 22% | 69% | [197] | |
| NSCLC | 10 | 100% (cytoplasmic) | [37] | |||||
| NSCLC | 40 | 27.5% | [198] | |||||
| NSCLC | 222 | 98.2% | [174] | |||||
| Lung AdCa | 5 | 20% | 60% | 20% | 40% | 20% | 60% | [167] |
| Lung squamous | 5 | 0% | 20% | 20% | 0% | 0% | 0% | [167] |
| Lung (unknown subtype) | 6 | 100% (cytoplasmic) | [37] | |||||
| Oesophageal | 5 | 20% | 20% | 20% | 20% | 40% | 0% | [167] |
| Gastric | 5 | 60% | 80% | 60% | 80% | 80% | 60% | [167] |
| Gastric | 23 | 57%/50% ‡ | [199] | |||||
| Gastric | 98 | 71% | [200] | |||||
| Gastric | 11 | 100% (cytoplasmic) | [37] | |||||
| Prostate | 5 | 0% | 80% | 20% | 20% | 20% | 0% | [167] |
| Prostate | 12 | 92% (cytoplasmic) | [37] | |||||
| Prostate | 165 | 65% (with 85% stromal staining which increased in Gleason stage) | [201] | |||||
| Renal cell | 5 | 0% | 20% | 20% | 0% | 0% | 20% | [167] |
| Renal (clear cell) | 71 | 42% | [202] | |||||
| Urothelial | 5 | 20% | 60% | 80% | 100% | 80% | 60% | [167] |
| Tongue | 5 | 0% | 0% | 0% | 0% | 60% | 0% | [167] |
| Larynx | 5 | 20% | 20% | 0% | 0% | 40% | 60% | [167] |
| Nasopharyngeal | 111 | ULBP4 only measured and was reduced in tumour versus normal tissue | [181] | |||||
| Thyroid papillary | 5 | 60% | 80% | 60% | 80% | 80% | 10% | [167] |
| Thyroid follicular | 5 | 33% | 100% | 100% | 67% | 0% | 10% | [167] |
| Skin | 5 | 20% | 0% | 0% | 0% | 40% | 20% | [167] |
| Thymoma | 36 | Widespread expression of all ligands; % not provided | [203] | |||||
| HCC | 5 | 40% | 100% | 60% | 40% | 60% | 10% | [167] |
| HCC | 10 | 60% (RT-PCR) | [204] | |||||
| HCC | 96 | 78% (not detected in surrounding noncancer tissue) ¶¶¶¶ | [161] | |||||
| HCC | 54 | †††† 46% 0% 0% 0% | [157] | |||||
| HCC | 6 | 50% (cytoplasmic) | [37] | |||||
| HCC | 143 | 100% MICA-positive but levels lower than in adjacent noncancer tissue | [205] | |||||
| Panc. AdCa | 25 | 63% (85% if patients had received neoadjuvant gemcitabine) | [154] | |||||
| Panc. AdCa | 103 | 89.3% (lower expression if poorly differentiated)**** | [206] | |||||
| Panc. AdCa | 9 | 88% (cytoplasmic) | [37] | |||||
| Panc. AdCa | 22 | 77% (more pronounced in poorly differentiated tumours) | [207] | |||||
| Panc. AdCa | 5 | 0% | 0% | 0% | 20% | 0% | 20% | [167] |
| Panc. AdCa | 22 | 100% † | 80% † | 87% ***† | 47% † | [100] ††† | ||
Abbreviations: ALL—acute lymphoblastic leukaemia; AML—acute myeloid leukaemia; CCA—cholangiocarcinoma; CML—chronic myeloid leukaemia; CLL—chronic lymphocytic leukaemia; GBM—glioblastoma; HCC—hepatocellular carcinoma; HGSOC—high-grade serous ovarian cancer; MFI—mean fluorescence intensity; NSCLC—non-small-cell lung cancer; Panc. AdCa.—pancreatic adenocarcinoma; T-ALL—T cell acute lymphoblastic leukaemia; TNBC—triple negative breast cancer. * Absolute percentage positivity not reported. These figures are for tumours with high-level expression of the indicated ligand. ** Note that this study reported the absence of ligand expression in normal control tissue, including fallopian tube epithelium and stromal cells. *** Co-staining of ULBP2/5/6. **** Positive staining noted in stroma in stage IV tumours. ¶ At least one NKG2DL family member present. ¶¶ MICA/B only analysed. ¶¶¶ Combined assessment of all NKG2DL. ¶¶¶¶ Expression intensity was reduced in more advanced tumours. § Percentages refer to GBM stem cells only. §§§ High-level expression only (as all tumours were classified as high or low). §§§§ Primary/metastatic. † Figures exclude weak staining. †† Combined ULBP2, -5 and -6. ††† These data were extracted from a poster presentation made by the authors and previously available on the Celyad Oncology website. †††† MICA was mainly detected in vascular endothelial cells of well- and moderately differentiated tumours, while ULBP1 was detected in tumour cells of well- and moderately differentiated tumours but not poorly differentiated tumours. ‡ MICA/MICB percentages.