Ocena ekspresji Foxp3 i RORgamma t w jednojądrzastych komórkach krwi obwodowej u chorych z rakiem krtani jako wskaźników zaawansowania zmian nowotworowych – badania wstępne

Abstract

The degree of activation of cells involved in cellular immune response against tumor antigens (cytotoxic lymphocytes Tc) as well as efficiency of the mechanisms which promote immunosuppression (Treg - regulatory cells CD4(+)CD25(+)Foxp3(+)) may determine the course of the neoplastic disease. The aim of this study was to assess the function of autologous peripheral blood mononuclear cells (PBMCs) involved in the immunological processes on the basis of expression of Foxp3 and RORgamma t molecules as well as analysis of the relationships with clinical and morphological features of the tumor (pT and pN stage, G feature, degree of invasiveness according to the TFG classification) in laryngeal carcinoma.The analysis included a group of 59 patients with verified squamous cell carcinoma of the larynx. In the pathologic evaluation pTNM classification criteria, depth of invasion and degree of histological differentiation were used. Expression levels of mRNA for Foxp3 and RORgamma t in peripheral blood mononuclear cells by quantitative analysis of the amplified product in real time (real-time RT(2)-PCR) were evaluated. The level of Foxp3 and RORgamma t protein expression by Western blot analysis was determined.In squamous cell carcinomas of the larynx, with the highest tumor aggressiveness the significantly highest level of mRNA and protein expression for Foxp3 molecule were observed. The severity of Foxp3 expression at both gene and protein level were positively linearly correlated with the degree of local extent of the tumor (pT3-4), depth of invasion (invasion of cartilage) and the degree of histological differentiation (low-differentiated tumors G3). In the study group of laryngeal cancers significantly lower level of RORgamma t expression in carcinomas with less invasive changes (pT1-2, high-differentiated tumors G1, carcinomas with microinvasion without evidence of invasion beyond the lamina propria) was also noted.The study results indicate the important role of immune cell activity as indicators of advancement of clinical and morphological changes in squamous cell carcinoma of the larynx.