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Published on: April 4, 2018
Clinical Impact of KIR2DS3 and KIR2DL3 Genes in Neuroblastoma Patients
Gülay Sezgin1, Özlem Görüroğlu Öztürk2, Ayşe Özkan1
1Division of Pediatric Oncology/Pediatric BMT Unit, Çukurova University Medical School, Adana, Turkey.
Objective:
Neuroblastoma is a common fatal tumor of childhood. Natural killer (NK) cells can exert direct cytotoxicity on tumor cells. The killer immunoglobulin-like receptor (KIR) family of NK cell receptors is involved in activation/inhibition of NK cells. In the KIR gene cluster, six of them (3DS1, 2DS1-5) encode receptors triggering activation, while seven of them (3DL1-3, 2DL1-3, 2DL5) encode receptors triggering inhibition. We aimed to assess the distribution of genetic polymorphisms of KIRs on the clinical course of neuroblastoma and provide guidance on potential therapeutic options.
Methods:
Our study group included 50 neuroblastoma patients and 100 healthy children as controls. Twenty-eight patients were boys, and twenty-two were girls; median age was 36 months. Fourteen patients had stage 1, 2, 3, or 4S disease, and 36 patients had stage 4 disease. Isolated DNA from the peripheral blood was amplified for sequence-specific oligonucleotide probe analysis of 16 KIR genes. The Fisher's exact test was used to evaluate the variation of KIR gene distribution.
Results:
All patients had a lower frequency of KIR2DS3 compared to the control group (p = 0.005). Evaluation of individual KIR genes/genotypes in patients with early stages (stage 1, 2, 3, and 4S) versus stage 4 disease revealed that the frequency of KIR2DS3 was increased in early stages (p = 0.023). Inhibitory KIR2DL3 was increased in the patient group compared to controls (p = 0.038). Furthermore, the frequency of KIR2DL3 was higher in stage 4 neuroblastoma patients compared to the patients with early stages (p = 0.023).
Conclusion:
Our data suggest a role for KIR2DS3 and KIR2DL3 in development of neuroblastoma. Thus, modulation of KIR2SD3 and/or KIR2DL3 expression or function might present a novel therapeutic strategy for neuroblastoma.
Insights
Killer immunoglobulin-like receptor (KIR) gene variants, specifically KIR2DS3 and KIR2DL3, are associated with neuroblastoma development. Modulating these KIR genes may offer new therapeutic strategies for this childhood cancer.
Area of Science:
- Immunology
- Pediatric Oncology
- Genetics
Background:
- Neuroblastoma is a frequent and often fatal childhood cancer.
- Natural killer (NK) cells and their Killer Immunoglobulin-like Receptors (KIRs) play a role in tumor surveillance.
- KIRs are crucial for NK cell activation and inhibition, influencing immune responses against cancer.
Purpose of the Study:
- To investigate the association between KIR gene polymorphisms and the clinical course of neuroblastoma.
- To explore potential therapeutic strategies targeting KIRs in neuroblastoma treatment.
Main Methods:
- A case-control study involving 50 neuroblastoma patients and 100 healthy controls.
- DNA analysis of 16 KIR genes using sequence-specific oligonucleotide probe analysis.
- Statistical evaluation of KIR gene distribution using Fisher's exact test.
Main Results:
- Patients with neuroblastoma showed a lower frequency of KIR2DS3 compared to controls (p = 0.005).
- KIR2DS3 was more frequent in early-stage neuroblastoma (stages 1, 2, 3, 4S) than in advanced stage 4 disease (p = 0.023).
- The inhibitory KIR2DL3 was more prevalent in neuroblastoma patients overall (p = 0.038) and in stage 4 patients compared to early stages (p = 0.023).
Conclusions:
- KIR2DS3 and KIR2DL3 gene variants are implicated in the pathogenesis of neuroblastoma.
- Targeting KIR2DS3 and/or KIR2DL3 function or expression presents a potential novel therapeutic avenue for neuroblastoma.
