Loss of T-cell receptor zeta chain and p56lck in T-cells infiltrating human renal cell carcinoma.
Cancer patients and mice bearing tumors develop a progressive immunosuppression manifested by a decreased delayed-type hypersensitivity, decreased T-cell lytic activity, diminished production of lymphokines, and a reduced T-cell proliferative response. The mechanisms underlying these changes are incompletely understood. We recently reported the presence of marked alterations in signal transduction in T-cells from mice bearing long-term (28-day) tumours. We hypothesized that a soluble product produced by the tumor or resulting from the immune response to tumor might be responsible for inducing the changes in T-cells. Tumor-infiltrating lymphocytes from patients with renal cell carcinoma tested here showed, in 10 of 11 cases, a marked decrease in the expression of the T-cell receptor zeta chain and in p56lck tyrosine kinase. The presence of major alterations in the tumor-infiltrating lymphocytes with only minor changes in the peripheral blood leukocyte T-cells supports the notion that the defects are induced by exposure to tumor. These results suggest that tumor-infiltrating lymphocytes may be compromised in their antitumor efficacy in patients with renal cell cancer.
Finke
J H
JH
Department of Immunology, Cleveland Clinic Foundation.
Zea
A H
AH
Stanley
J
J
Longo
D L
DL
Mizoguchi
H
H
Tubbs
R R
RR
Wiltrout
R H
RH
O'Shea
J J
JJ
Kudoh
S
S
Klein
E
E
D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000276:immunology; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry* / Q000276:immunology; D008565:Membrane Proteins / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*
D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)