The decreased expression of CD3 zeta chains in cancer patients is not reversed by IL-2 administration.
The mechanisms underlying the impaired immune response frequently observed in cancer patients are poorly understood. Recently, a decreased expression of the signal-transducing CD3 zeta chains has been shown to occur in patients with colorectal or renal-cell carcinoma. Here, we have investigated the expression of the zeta molecule on lymphocytes from patients with advanced cancers including renal-cell carcinoma (n = 21), hepatic colorectal carcinoma metastases (n = 6), head-and-neck squamous-cell carcinoma (n = 7) or miscellaneous tumors (n = 7), using flow cytometry analysis of PBMCs with monoclonal antibody specific for the cytoplasmic domain of the zeta chain. The same analysis was also performed with patients undergoing IL-2 therapy (from 5 days up to 3 months i.v. or s.c.). PBMCs from patients (n = 41) showed a significant decrease in expression of the zeta chains as compared to the levels found in lymphocytes from healthy controls (n = 15), which was not reversed by IL-2 administration. Together, these results suggest that an alteration in the expression of the zeta-chain-transducing element in PBMCs may be a common cause of progressive immunosuppression in advanced cancer patients and that IL-2 is not sufficient to reverse this situation in vivo.
Farace
F
F
Unité d'Immunologie Cellulaire, INSERM U333, Villejuif, France.
Angevin
E
E
Vanderplancke
J
J
Escudier
B
B
Triebel
F
F
D000951:Antigens, Neoplasm / Q000032:analysis*; D017252:CD3 Complex / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology; D015179:Colorectal Neoplasms / Q000276:immunology; D004334:Drug Administration Schedule; D006258:Head and Neck Neoplasms / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008565:Membrane Proteins / Q000032:analysis*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*
D000951:Antigens, Neoplasm; D017252:CD3 Complex; D007376:Interleukin-2; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain