T lymphocytes infiltrating renal cell carcinoma have a reduced expression of transferrin receptor.
T-cell responses have been reported to be impaired in cancer patients, and lymphocytes infiltrating human tumors (T-TIL) appear to be more affected than those in the peripheral blood. T-TIL display a poor proliferative response when compared to peripheral blood T (T-PBL) cells that show a strong response to all stimuli. Here we report that T-TIL from patients with renal cell carcinoma (RCC) also have a defect in transferrin receptor (TfR) expression that is not present in T-PBL cells. Immunocytometry studies (dual staining for CD3 epsilon and TfR) demonstrated that autologous T cells from the peripheral blood but not from the tumor expressed TfR following stimulation with IL2, anti-CD3 or PHA. Expression of TfR correlated with the capacity of T cells from the blood and tumor to proliferate. Gene expression studies using reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that TfR mRNA levels in T-TIL were undetectable or low relative to T-PBL following stimulation. The failure to detect TfR mRNA in T-TIL after stimulation was not due to a shift in kinetics of mRNA accumulation since TfR mRNA was not detectable at any of the times tested (4, 12, 24 and 36 hr). The defect in TfR gene expression is selective since IL2R alpha gene expression was induced in T-TIL. Because IL2 binding to its receptor results in TfR expression, the defect in TfR induction in T-TIL appears to be distal to IL2R alpha expression. Our studies illustrate another alteration in T-TIL that is not observed in T cells from the peripheral blood. The absence of TfR gene expression may contribute to the poor proliferative response of T cells from the tumor.
Kudoh
S
S
Department of Immunology, Cleveland Clinic Foundation, OH 44195.
Stanley
J
J
Edinger
M G
MG
Tubbs
R R
RR
Klein
E
E
Bukowski
R M
RM
Finke
J H
JH
D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000648:ultrastructure*; D015870:Gene Expression; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000648:ultrastructure*; D008213:Lymphocyte Activation / Q000502:physiology; D016246:Lymphocytes, Tumor-Infiltrating / Q000502:physiology* / Q000648:ultrastructure*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011990:Receptors, Transferrin / Q000235:genetics*; D013601:T-Lymphocytes / Q000502:physiology* / Q000648:ultrastructure*
D012333:RNA, Messenger; D011990:Receptors, Transferrin