Zbornik - Društvo genetičara Srbije

184 ZBORNIK ABSTRAKATA III KONGRESA GENETIÈARA SRBIJE V-Usm-1
Subotica, 30. novembar - 4. decembar 2004.
ANALIZA KLONALNOSTI T-ÆELIJA U TUMORSKIM UZORCIMA
BOLESNICA SA KARCINOMOM DOJKE
Bojana Cikota 1 , Mirjana Brankoviæ-Magiæ 2 i Z. Magiæ 1
1
Institut za medicinska istraivanja, Vojnomedicinska akademija, Beograd
2
Institut za onkologiju i radiologiju Srbije, Beograd
Rezultati brojnih istraivanja su pokazali da razlièiti tumori, ukljuèujuæi i tumore dojke,
mogu stimulisati specifièni T-æelijski antitumorski odgovor. Prepoznavanje tumor-specifiènog
antigena (kojeg tumorska æelija eksprimira endogeno ili egzogeno kao
peptid prezentovan putem antigen-prezentujuæih æelija) rezultuje klonalnom ekspanzijom
i diferencijacijom naivnih CD8 + T-æelija u aktivirane efektorske æelije koje uèestvuju u
ubijanju tumorskih æelija. U ovom istraivanju je analizirana klonalnost T-æelija u
tumorskim uzorcima 54 bolesnice sa karcinomom dojke. Na osnovu prisustva/odsustva
metastaza u regionalnim limfnim èvorovima bolesnice su klasifikovane u grupu N+
(prisutne metastaze; n=25) ili N0 (bez metastaza; n=16). Analiza klonalnosti T-æelija se
zasnivala na PCR amplifikaciji dela rearaniranog gena za lanac TCR-a i PAGE.
Prisustvo monoklonalne/oligoklonalne (M/O) populacije T-æelija je detektovano u 9
bolesnica iz N+ i 6 bolesnica iz N0 grupe. U svim analiziranim grupama (N + +N0, N+,
N0) nije uoèena statistièki znaèajna razlika u uèestalosti relapsa izmeðu bolesnica sa M/O
u odnosu na bolesnice sa poliklonskom T-æelijskom populacijom. Poreðenjem duine
perioda bez bolesti (DFI) tokom prve dve godine u bolesnica sa M/O T-æelijama u
odnosu na bolesnice sa poliklonskom populacijom je dobijena statistièki znaèajna razlika
graniène vrednosti samo u N+ grupi. Bolesnice sa M/O T-æelijama su imale kraæi DFI od
bolesnica sa poliklonskom populacijom. Ova razlika nije uoèena kada se analiza
zasnivala na periodu praæenja duem od 2 godine.
Dobijeni rezultati ukazuju da su populacije tumor infiltrirajuæih limfocita uglavnom
poliklonalne.
ANALYSIS OF T-CELL CLONALITY PATTERN IN TUMOR SAMPLES OF
BREAST CANCER PATIENTS
Numerous experimental evidences confirm that different tumors, including breast carcinomas,
can stimulate specific T-cell mediated immune response. Recognition of tumor-associated
antigen (expressed endogenously by tumor cells or exogenously as peptide
presented by antigen-presenting cells) results in the clonal expansion and differentiation
of naive CD8+ T-cells into activated effector cells that mediate tumor cell killing. In
this study we have analyzed pattern of T-cell clonality in tumor samples of 54 breast cancer
patients classified as lymph node-negative – N0 (n=16) or lymph node-positive – N+
(n=25). Analysis of T-cell clonality was based on PCR amplification of rearranged TCR
chain gene followed by PAGE.
Monoclonal/oligoclonal (M/O) T-cell populations were found in 9 of N + and6ofN0 breast cancer patients, respectively. In all analyzed groups (N + +N0, N+, N0), incidence
of relapse was not significantly different between patients with M/O T-cells vs patients
with polyclonal T-cells. Comparison of disease free interval (DFI) between the patients
divided according to the presence of TCRã monoclonality/oligoclonality showed
board-line significant difference only in the group of N+ patients within first 24 months
of follow-up. Patients with M/O T-cell population had shorter DFI than patients with
polyclonal T-cell population. Concerning the complete follow-up in the same group of
patients, this difference was not observed.
Our results imply that tumor infiltrating T-cells are usually polyclonal.