Küçük hücreli dışı akciğer kanserlerinde hafıza CD8 T hücre fonksiyonunun rolü
Küçük Resim Yok
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Tekirdağ Namık Kemal Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Küçük hücreli dışı akciğer kanseri (KHDAK) en ölümcül tümörlerden biridir. Geleneksel terapötik stratejilerin başarısızlığı göz önüne alındığında, immünoterapi, ameliyat edilebilir ve ilerlemiş hastalığı olan hastaların hayatta kalma oranını artırabilecek umut verici bir tedavi yöntemi olarak ortaya çıkmıştır. Tez çalışmamız kapsamında, metastatik evrede birinci basamak tedavide, kemoterapi planlanan akciğer kanseri tanısı almış hastalarımızda başlangıç T lenfosit alt tiplerinin tedavi yanıtı üzerine etkisinin değerlendirilmesi amaçlanmıştır. KHDAK tanısı almış 44 hastaya ait periferik kan örneklerindeki T lenfositlerinin akım sitometri ile immünfenotiplemesinde işaretlenmiş monoklonal antikor paneli kullanılarak incelendi. Çalışmamızda, en çok gözlenen alt tipi %80'den fazla ortanca değer olan CD28(+) CD27(+) alt tipi iken CD28(+) CD27(-) alt tipi %6 ve daha az oranda CD28(-) CD27(+) ve CD28(-) CD27(-) alt tipleri gözlendi. KT yanıtı olan ve olmayan gruplar arasında hastaların tedavi öncesi NLR (p=0,033) ve TLO (p=0,036) değerleri arasında istatistiksel anlamlılık tespit edildi. Tek değişkenli modelde genel sağkalım süresini öngörmede CD4 hücrelerinde PD1 ve CD28(+) CD27(+), CD8 hücrelerinde PD1, CD28(+) CD27(+), CD28(-) CD27(-), LDH ve Hemoglobin parametrelerinde istatistiksel anlamlılık gözlenmiştir (p<0,05). Çok değişkenli indirgenmiş modelde genel sağkalım süresini öngörmede CD4 hücrelerinde PD1'in etkisi gözlenmiştir (p<0,05). Progresyonsuz sağkalım süresini öngörmede CD4 hücrelerinde CD28(+) CD27(+) ve CD28(-) CD27(+), CD8 hücrelerinde CD28(+) CD27(+), LDH ve mutlak lenfosit değerleri arasında ilişki tespit edilmiştir (p<0,05). Multivariant analiz neticesinde de progresyonsuz sağkalım süresini öngörmede CD4 hücrelerinde PD1, CD8 hücrelerinde CD28(+) CD27(+) ve mutlak lenfosit sayısı arasında anlamlılık gözlenmiştir (p<0,05). Sonuç olarak, özellikle CD28(-) olan hastaların daha kısa sağkalım oranına sahip olması ve hedef belirteçlerdeki azalmanın/yok olmanın spesifik olarak malignitenin agresifliğini artırmaya yatkın olduğu düşünülmektedir.
Non-small cell lung cancer (NSCLC) is one of the deadliest tumors. Given the failure of conventional therapeutic strategies, immunotherapy has emerged as a promising treatment modality that is operable and can improve the survival rate of patients with advanced disease. In our thesis study, we investigated the impact of initial T lymphocyte subtypes on treatment response in patients with lung cancer who were scheduled to undergo chemotherapy. T lymphocytes in peripheral blood samples from 44 patients diagnosed with NSCLC were analyzed by flow cytometry and immunophenotyping using a labeled monoclonal antibody panel. In our study, the most frequently observed subtype was the CD28(+)-CD27(+) subtype with a median value of over 80%, while the CD28(+)-CD27(-) subtype was 6% and fewer than CD28( -)-CD27(+) and CD28(-)-CD27(-) subtypes were observed. Statistical significance was observed between the pre-treatment NLR (p=0.033) and TLR (p=0.036) values of patients in the KT response and non-KT response groups. In the univariate model, statistical significance was found for the parameters PD1 and CD28(+) CD27(+) on CD4 cells, PD1, CD28(+) CD27(+), CD28(-) CD27(-), LDH and hemoglobin on CD8 cells in predicting overall survival (p<0.05). In the multivariate reduced model, the effect of PD1 on CD4 cells was observed in predicting overall survival (p<0.05). In predicting disease-free survival, a correlation was observed between CD28(+) CD27(+) and CD28(-) CD27(+) on CD4 cells, CD28(+) CD27(+) on CD8 cells, LDH and absolute lymphocyte levels (p<0.05). In multivariate analysis, significance was found between PD1 on CD4 cells, CD28(+) CD27(+) on CD8 cells and absolute lymphocyte count in predicting disease-free survival (p<0.05). It is therefore assumed that patients, especially those with CD28(-), have a shorter survival rate and that the decrease or absence of target markers increases the aggressiveness of the malignancy.
Non-small cell lung cancer (NSCLC) is one of the deadliest tumors. Given the failure of conventional therapeutic strategies, immunotherapy has emerged as a promising treatment modality that is operable and can improve the survival rate of patients with advanced disease. In our thesis study, we investigated the impact of initial T lymphocyte subtypes on treatment response in patients with lung cancer who were scheduled to undergo chemotherapy. T lymphocytes in peripheral blood samples from 44 patients diagnosed with NSCLC were analyzed by flow cytometry and immunophenotyping using a labeled monoclonal antibody panel. In our study, the most frequently observed subtype was the CD28(+)-CD27(+) subtype with a median value of over 80%, while the CD28(+)-CD27(-) subtype was 6% and fewer than CD28( -)-CD27(+) and CD28(-)-CD27(-) subtypes were observed. Statistical significance was observed between the pre-treatment NLR (p=0.033) and TLR (p=0.036) values of patients in the KT response and non-KT response groups. In the univariate model, statistical significance was found for the parameters PD1 and CD28(+) CD27(+) on CD4 cells, PD1, CD28(+) CD27(+), CD28(-) CD27(-), LDH and hemoglobin on CD8 cells in predicting overall survival (p<0.05). In the multivariate reduced model, the effect of PD1 on CD4 cells was observed in predicting overall survival (p<0.05). In predicting disease-free survival, a correlation was observed between CD28(+) CD27(+) and CD28(-) CD27(+) on CD4 cells, CD28(+) CD27(+) on CD8 cells, LDH and absolute lymphocyte levels (p<0.05). In multivariate analysis, significance was found between PD1 on CD4 cells, CD28(+) CD27(+) on CD8 cells and absolute lymphocyte count in predicting disease-free survival (p<0.05). It is therefore assumed that patients, especially those with CD28(-), have a shorter survival rate and that the decrease or absence of target markers increases the aggressiveness of the malignancy.
Açıklama
Sağlık Bilimleri Enstitüsü, Tümör Biyolojisi ve İmmünolojisi Ana Bilim Dalı
Anahtar Kelimeler
Allerji ve İmmünoloji, Allergy and Immunology ; Onkoloji
