Küçük hücre dışı akciğer kanseri hastalarında doğal lenfoid hücre alt gruplarındaki değişiklikler ve tümör gelişimindeki olası rolleri

Öz

Giriş: Küçük hücre dışı akciğer kanseri (KHDAK) tüm dünyada ciddi morbidite ve mortaliteye neden olmaktadır. Özellikle son yıllarda önemi daha iyi anlaşılan ILC (doğal lenfoid hücreler) alt gruplarındaki değişikliklerin tümör gelişiminde önemli rol oynayabileceği öne sürülmüştür. Bu çalışmada KHDAK hastalarında periferik kan ve tümörü drene eden mediastinal lenf nodlarındaki ILC alt grupları incelenmiştir. Gereç ve Yöntemler: Çalışmamıza video yardımlı mediastinal lenfadenektomi uygulanan T1-4N0-2M0 evreli ve daha önce sistemik kemoterapi/radyoterapi almamış 13 KHDAK hastası ve 14 sağlıklı kontrol incelenmiştir. Periferik kan ve mediastinal lenf nodundan izole edilen lenfositlerde NK hücre ile ILC alt grupları akan hücre ölçer ile analiz edilmiştir. Sonuç: KHDAK olguların kan örneklerinde total NK hücre oranı tümör drene eden lenf noduna kıyasla artmıştır. CD56dimCD16- tükenmiş NK hücrelerin oranı ise lenf nodu örneklerinde KHDAK hastaların kan örneklerine kıyasla daha yüksek saptanmıştır. KHDAK olguların kanında ILC1 oranı kontrol grubuna kıyasla daha düşük, ILC2 ve ILC3 alt gruplarının oranı ise daha yüksek bulunmuştur. Buna karşın KHDAK olguların mediastinal lenf nodunda aynı hastaların kan örneklerine göre ILC2 oranı düşük, ILC3 oranı ise yüksektir. KHDAK hastaların lenf nodunda NKp44-ILC3 oranı artmışken, NKp44+ILC3 oranı azalmıştır. Tartışma: KHDAK hastalarında ILC1 hücre oranındaki azalma bozulmuş anti-tümöral immünitenin önemli bir göstergesidir. Tümör büyümesinde rol oynadığı düşünülen IL-17’yi salgılayan NKp44-ILC-3 hücre grubunun bu hastalarda artmış olması, bu hücrelerin tümör gelişiminde rolü olabileceğini düşündürmektedir. Bu bulgular ILC hücre ailesinin akciğer kanseri patogenezinde önemli rollere sahip olduğunun altını çizmektedir.

Anahtar Kelimeler

• KHDAK
• NK hücre
• ILC1
• ILC2
• ILC3
• immünoterapi

The importance of alterations in innate lymphoid cell subsets in patients with non-small cell lung cancer and their role in tumorigenesis

Abstract

Objective. Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related morbidity and mortality. Diverse functions of innate lymphoid cells (ILCs) and NK cell subsets are investigated thoroughly in cancer immunotherapy. ILC and recently described NK cell subsets in NSCLC patients’ blood samples and tumor draining lymph nodes were investigated. Methods. The study included chemotherapy and/or radiotherapy-naive NSCLC patients with clinical stage T1-4N0-2M0 who underwent video-assisted mediastinal lymphadenectomy and 14 healthy controls. Mononuclear cells were isolated from peripheral blood of both groups and mediastinal lymph nodes of NSCLC patients. NK cells and ILC subsets were analyzed by flow cytometry. Results. Total NK cells are shown to be increased in peripheral blood of NSCLC patients compared to lymph nodes while the ratio of CD56dimCD16- exhausted NK cells is higher in lymph nodes than in blood samples of NSCLC patients. Compared to control group, peripheral blood ILC1 cells were lower in NSCLC patients, however ILC2 and ILC3 cells were significantly increased. However, mediastinal lymph nodes of NSCLC patients had decreased ratio of ILC2 and increased ratio of ILC3 cells than in peripheral blood of patients. NSCLC patients had significantly increased ratio of NKp44-ILC3 cells and decreased ratio of NKp44+ILC3 in lymph nodes. Conclusion. Decreased ratio of ILC1 cells is an important indicator of impaired anti-tumoral response. Increased in the ratio of NKp44-ILC3 cells in NSCLC patients may potentially contribute to tumor progression. These findings highlight the distinct roles of ILCs, which play a pivotal role in the pathogenesis of lung cancer.

Keywords

• NSCLC
• NK cells
• ILC1
• ILC2
• ILC3
• Immunotherapy

Kaynakça

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