Koncentracije citokina u serumu kod pacijenata sa planocelularnim karcinomom larinksa

Abstract

Uvod: Nastanak i progresija malignog tumora podrazumevaju nekontrolisanu ćelijsku transformaciju, invazivnost, angiogenezu i sposobnost metastaziranja. Epidemiološki podaci ukazuju da je pušenje najznačajniji etiološki faktor za nastanak planocelularnog karcinoma larinksa (engl. Laryngeal squamous cell carcinoma, LSCC), a u izvesnoj meri i upotreba alkohola. Brojne kliničke i ekperimentalne studije pokazuju da je nastanak malignog tumora rezultat poremećenog imunskog odgovora. Citokini deluju kao medijatori inflamacije i imunskog odgovora i predstavljaju potencijalnu metu antitumorske terapije. Diferencijacija pomagačkih T limfocita (engl. T helper, Th) prema funkcionalno različitim subpopulacijama (Th1, Th2, Th17) praćena je produkcijom različitih citokina. Jedan od pretpostavljenih mehanizama u nastanku malignog tumora je poremećaj u odnosu Th1 (Tip 1) i Th2 (Tip 2) imunskog odgovora. Hipoteza prethodnih studija bila je da povećani Th2 (Tip 2), a smanjeni Th1 (Tip 1) imunski odgovor vodi nastanku malignog tumora. Takođe, brojne studije ukazuju na povezanost hronične inflamacije i malignih tumora. Podaci u medicinskoj literaturi o ulozi interleukina (IL)-17 u karcinogenezi se dosta razlikuju među sobom, a broj radova koji se tiče povezanosti LSCC i IL-17 je mali. Detaljnim pregledom medicinske literature nismo našli studiju koja je ispitivala povezanost serumskih koncentracija IL-22 i LSCC. Ciljevi: Cilj ove studije bio je merenje serumskih koncentracija trinaest citokina (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, IL-22, IFN-γ i TNF-α) kod zdravih ispitanika i pacijenata sa LSCC. Metode: Naša studija je uključila 59 pacijenata sa LSCC i 44 zdravih ispitanika. Od svih ispitanika uzeto je 5 ml periferne venske krvi kao i podaci o pušenju i upotrebi alkohola. Koncentracije ispitivanih citokina merene su u svakom od uzoraka seruma metodom protočne citometrije (flow-cytometry) uz korišćenje komercijalnog protočnog citometrijskog kita (Flow Cytomix, Bender Med Systems, USA). Poređenje rezultata vršeno je u odnosu na prisustvo malignog tumora u larinksu, subregion larinksa zahvaćen tumorom, stadijum bolesti, histološki gradus tumora, upotrebu alkohola i pušenje.

Introduction: Malignant tumor promotion and progression involve uncontrolled cellular transformation, invasion, angiogenesis and metastasis. Laryngeal squamous cell carcinoma (LSCC) is widely connected with tobacco consumption and alcohol misuse. Clinical and experimental studies have suggested that malignant tumor development is a result of altered immunity and inflammatory reaction. Cytokines, being the mediators of the communication between tumor cells and host immune cells, were linked to malignant transformation. Helper T (Th) cells, as part of the adaptive human immunity, play a key role in the immune response. Differentiation of the Th cells is followed by cytokine production. Many recently published reports refer to the skewing of the Th1-Th2 (Type 1-Type 2) balance towards Th2 (Type 2) cytokines in cancer patients, while most proinflammatory cytokines were connected with tumor development. In the published literature data on interleukin (IL)-17 serum levels in carcinogenesis is inconsistent while we didn’t find the study on IL-22 serum levels in LSCC patients. Objectives: The aim of this study was to measure serum levels of thirteen different cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, IL-22, IFN-γ, and TNF-α) in healthy subjects and in LSCC patients, in order to identify potential biomarkers that indicate tumor presence and progression. Methods: Study included 59 LSCC patients and 44 healthy controls. Peripheral blood samples (5 ml) and data on self-reported tobacco and alcohol consumption were collected from all the participants. Multiplex analysis of interleukin IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, IL-22, IFN-γ, and TNF-α by commercial flow cytometric kit (FlowCytomixTM Multiple Analyte Detection System) was performed. Results were compared according to the presence of laryngeal carcinoma, T stage, nodal involvement, histologic grade of the tumor, subsite of the larynx, active smoking status and alcohol consumption.