Defective granzyme B gene expression and lytic response in T lymphocytes infiltrating human renal cell carcinoma.
Granzyme B is a protein thought to play a pivotal role in the cytolytic functions of T cells. In view of this, the inducibility of this gene in freshly isolated T cells (T-TILs) infiltrating human renal cell carcinoma (RCC) in vitro was examined by using the reverse transcriptase-polymerase chain reaction (RT-PCR). A reduction in granzyme B messenger RNA (mRNA) expression in stimulated T-TILs from five of nine patients with RCC compared with autologous peripheral blood T cells was noted. The reduced expression was observed after multiple stimuli including anti-CD3 antibody, interleukin-2 (IL-2), and phytohemagglutinin (PHA). Because CD8+ T cells represent the predominant cytotoxic population, the ability of this cell population to express granzyme B mRNA after stimulation also was examined. When compared with CD8+ peripheral blood lymphocytes (T-PBLs) from patients with RCC and normal donors, the induction of granzyme B mRNA was reduced in CD8+ T-TILs. CD8+ T-TILs also had lower non-major histocompatibility complex (MHC)-restricted cytotoxic activity than did CD8+ T-PBLs against both Daudi cells and allogeneic RCC cell lines. These results show that in a subset of patients with RCC, depressed lytic activity of CD8+ TILs compared with CD8+ PBLs is present. Reduced granzyme B mRNA expression also was noted in selected patients.
Kudoh
S
S
Department of Immunology, Cleveland Clinic Foundation 44195, USA.
Redovan
C
C
Rayman
P
P
Edinger
M
M
Tubbs
R R
RR
Novick
A
A
Finke
J H
JH
Bukowski
R M
RM
D002292:Carcinoma, Renal Cell / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression; D053804:Granzymes; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012194:RNA-Directed DNA Polymerase; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D012333:RNA, Messenger; D012194:RNA-Directed DNA Polymerase; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases