Table 1.
NKp30 splice variants
| Article | Model/targets | Conditions/effectors | Results |
|---|---|---|---|
| Delahaye et al. (Nat. Med. 2011) [26] | INFγ and TNFα, secretion following NKp30 ligation or recognition of iDCs or mDCs or HeLa cells, IL-12p7 secretion by mDCs. Lysis of K562. Secretion of IL-10 follow incubation with HeLa cells or iDCs. Association with CD3ζ, activation of mitogen-activated protein | NKL | NKp30 ligation or HeLa cells had no effect on INFγ secretion, co-incubation with iDCs or mDCs led to secretion of TNFα, mDCs secretion of IL-12p7. No K562 lysis. Low effect on IL-10 secretion |
| NKL overexpressing NKp30a | NKp30 ligation or HeLa cells increase INFγ secretion, co-incubation with iDCs or mDCs increases the secretion of INFγ and TNFα, increased mDCs secretion of IL-12p7. High K562 lysis. Low IL-10 secretion. Strong association with CD3ζ. Weak activation of p38 mitogen-activated protein kinase | ||
| NKL overexpressing NKp30b | NKp30 ligation but not HeLa cells increases INFγ secretion, co-incubation with iDCs or mDCs increases the secretion of INFγ and TNFα, increased mDCs secretion of IL-12p7. Moderate K562 lysis. No effect on IL-10 secretion. Strong association with CD3ζ. Weak activation of p38 mitogen-activated protein kinase | ||
| NKL overexpressing NKp30c | NKp30 ligation or HeLa cells had no effect on INFγ secretion, co-incubation with iDCs or mDCs led to secretion of TNFα, mDC secretion of IL-12p7. No K562 lysis. Increased IL-10 secretion. Weak association with CD3ζ. Strong activation of p38 mitogen-activated protein kinase | ||
| qPCR analysis of NKp30 splice variants using TaqMan in healthy volunteers or individuals with GIST. NKp30 ligation effect on TNFα, CD107a, IκBα degradation. Survival of GIST patients | NKp30a/b profile | Dominant expression of NKp30b, similar levels of NKp30a and NKp30c. Higher levels of TNFα, and CD107a, faster IκBα degradation relative to NKp30C. Associated with increased survival of GIST patients | |
| NKp30c profile | Dominant expression of NKp30b, higher levels of NKp30c relative to NKp30a. lower levels of TNFα, and CD107a, delayed IκBα degradation relative to NKp30a/b. Associated with reduced survival of GIST patients | ||
| Prada et al. (Oncoimmunology 2013) [27] | 89 Therapy-naive HIV-1-infected individuals checked for spontaneous disease progression | NKp30 splice variants profiles | No role in the outcome of HIV-1 infection |
| Semeraro and Rusakiewicz et al. (Sci Transl Med 2015) [31] | NKp30 protein expression, qPCR analysis using TaqMan of NKp30 splice variants in neuroblastoma patients | Healthy volunteers (HV) vs. localized disease vs. metastatic disease | Increased NKp30 levels in localized disease PBMC. Reduced NKp30 levels in metastatic disease BM. NKp30 splice variants; ΔBC and ΔAC but not ΔAB were reduced in metastatic disease. ΔBC in patients with minimal residual disease correlate with progression-free survival |
| Shemesh and Tirosh et al. (Front. Immunol. 2015) [35] | qPCR analysis of NKp30 splice variants using SYBR and correlation to INFγ, TNFα IL-10, PLGF and VEGF-A in 1st trimester placenta tissue and PBMC from elective, sporadic, and recurrent abortions | PBMC | No significant change was observed in NKp30 mRNA levels between the study groups. NKp30c but not NKp30a or NKp30b, was higher in PBMC from sporadic + recurrent abortions. No correlation to INFγ, TNFα IL-10, PLGF and VEGF-A |
| Placenta tissue | No significant change was observed in NKp30 mRNA levels between the study groups. NKp30a and NKp30b but not NKp30c were higher in placenta tissue from sporadic + recurrent abortions. NKp30a and NKp30b show strong positive correlation to INFγ, TNFα IL-10 and VEGF-A in the elective abortions group. Strong negative correlation to PLGF in the sporadic or recurrent groups | ||
| Mantovani et al. (Immunology. 2015) [28] | Expression of NKp30 protein and NKp30 splice variants using TaqMan in PBMC, redirected functional assay with P815 cells using anti-NKp30 mAb | Healthy donors (HD) | Predominant NKp30a/b profile |
| HCV + patients | Reduced NKp30. Predominant NKp30a/b profile; subdivided into: HCV-1 cluster (similar to HD) or HCV-2 cluster (reduced NKp30 levels and higher activity associated with relatively higher levels of NKp30a) | ||
| Siewiera et al. (Nature communications 2015) [34] | qPCR analysis of NKp30 splice variants using SYBR Green, mAb ligation of NKp30 co-ligation of NKp30 and NKp46, immune synapse formation | Fresh isolated Human decidual NK cells | Low levels of NKp30a and NKp30b, high levels of NKp30c, no effect on CD107a, and co-ligation with NKp46 had no effect. Low immune synapse formation |
| IL-15; overnight stimulation, isolated human primary NK cells | High levels of NKp30a and NKp30b, low levels of NKp30c, increased CD107a, co-ligation with NKp46 had no effect. High immune synapse formation | ||
| Cytokine stimulation of isolated human primary NK cells for 6 days. NKp30 splice variant analysis by qPCR using SYBR Green. Expression of NKp44 splice variants relative to pNK cells cultured in cytokine free medium with or without lysis of P815 target cells or cytokine secretion after mAb ligation of NKp30 | IL-15 | High levels of NKp30a and NKp30b relative to NKp30c | |
| IL-18 | High levels of NKp30a and NKp30b relative to NKp30c | ||
| IL-15/IL-18 | High levels of NKp30a and NKp30b relative to NKp30c, increased lysis, increased secretion of TNFα/IFNγ/CCL3/VEGF-A | ||
| TGFβ | Reduced NKp30 mRNA, High levels of NKp30c relative to NKp30a and NKp30b | ||
| TGFβ/IL-15 | High levels of NKp30b and NKp30c relative to NKp30a | ||
| TGFβ/IL-18 | Reduced NKp30 mRNA, High levels of NKp30c relative to NKp30a and NKp30b | ||
| TGFβ/IL-15/IL-18 | High levels of NKp30b and NKp30c relative to NKp30a, increased lysis, increased secretion of TNFα/IFNγ/CCL3/VEGF-A | ||
| Shemesh et al. (Oncotarget 2016) [37] | RNAseq data of Breast, Lung, Cervical/Uterine, Kidney, Gastrointestinal tract organs, Gastrointestinal (GI) tract accessory organs solid tumors (TCGA) | Solid tumor samples vs. matched normal tissue | Predominant NKp30a/b profile in the tumor and normal tissues, comparison of matched tumor and normal tissue samples revealed shift between NKp30a/b to NKp30c and NKp30c to NKp30a/b |
| Messaoudene et al. (Oncoimmunology 2016) [29] | Expression of NKp30 protein and qPCR analysis NKp30 splice variants using TaqMan in PBMC, transcript levels of NKp46 | Healthy volunteers (HV) | Positive for NKp30a, NKp30b and NKp30c |
| Melanoma patients | Reduced NKp30 levels relative to HV, similar NKp30 splice variant profile relative to HV; higher NKp30c in patients with stage IV. No effect on patient survival from day of sampling. NKp46 levels subdivided stage IV patients to NKp46high and NKp46low; patient survival positively correlated with NKp46 levels | ||
| Long-term survivor (LS) melanoma patients | High NKp46 levels as compared to HV and stage IV patients. With higher expression of NKp30a | ||
| Rusakiewicza et al. (Oncoimmunology 2017) [33] | qPCR analysis of NKp30 splice variants using TaqMan in PBMC and GIST tumorsamples | Metastatic GIST patients relative to HD | NKp30 splice variants; ΔBC and ΔAC but not ΔAB were reduced. ΔBC was best predictor for overall patient survival and event-free survival |
| Fend et al. (Oncoimmunology 2017) [32] | qPCR analysis of NKp46 and NKp30 mRNA and splice variant profiles using TaqMan | PBMC from NSCLC patients relative to HD | Reduced NKp46 and NKp30 significantly elevated ΔAB and ΔAC, reduced ΔBC. Low levels of NKp30 had negative prognostic impact on overall survival with no effect of ΔAB, ΔAC, and ΔBC |