Alteration of cellular mediated cytotoxicity, T cell receptor zeta (TcR zeta) and apoptosis related gene expression in nasopharyngeal carcinoma (NPC) patients: possible clinical relevance.
We have investigated apoptosis related gene expression in tumour cells, phenotype and function of blood mononuclear cells at diagnosis in relation to clinical response in three patients with nasopharyngeal carcinoma (NPC). We have focused our study on the Epstein Barr virus latent membrane protein-1 (LMP-1) and Bcl-2 expression in the tumour cells, the essential signal-transducing zeta molecule of T cell receptor (TcR zeta) and cellular mediated cytolysis of the blood mononuclear cells. The carcinoma cells of the patients were Bcl-2 negative. They were heterogeneous with regard to the expression of LMP-1 and the number of proliferating or apoptotic cells. Decrease in the expression of mature T cells (CD3, CD4, and CD8), TcR zeta and cellular mediated cytotoxicity was detected in blood mononuclear cells of the patients. IL-2 up-regulated these phenotypes and the cytolytic capacity of the blood mononuclear cells. The patient with LMP-1 negative carcinoma cells, down-regulated TcR zeta expression and impaired IL-2 mediated cytolysis, had the worst clinical outcome. Another patient with low apoptotic, highly proliferating and LMP-1 positive carcinoma cells had recurrent disease only in the irradiated area. Interestingly, NPC with high apoptotic and few LMP-1 expressing cells was detected in the patient with a normal level of TcR zeta expression and cytolytic functions in blood mononuclear cells at the time of diagnosis. After combination treatment with chemotherapy followed by radiotherapy, this patient is still alive with complete remission and disease-free at 36 months. Suppression of the immunological functions may occur in NPC patients. Our study suggests that the immunological functions and apoptosis related gene expression in the carcinoma cells may be used as prognostic factors and help in the decision of therapy of patients with nasopharyngeal cancer.
Laytragoon-Lewin
N
N
Department of Oncology/Pathology, Karolinska Hospital, Stockholm, Sweden.
Porwit-MacDonald
A
A
Mellstedt
H
H
Lewin
F
F
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics*; D002352:Carrier Proteins / Q000032:analysis; D002478:Cells, Cultured; D002945:Cisplatin / Q000008:administration & dosage; D003598:Cytoskeletal Proteins; D003602:Cytotoxicity, Immunologic; D005472:Fluorouracil / Q000008:administration & dosage; D019672:Genes, T-Cell Receptor; D006801:Humans; D007111:Immunity, Cellular; D007372:Interferons / Q000627:therapeutic use; D007376:Interleukin-2 / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins; D007633:Keratins / Q000032:analysis; D060588:LIM Domain Proteins; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D008565:Membrane Proteins; C484380:PDLIM7 protein, human; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D007633:Keratins; D007372:Interferons; D002945:Cisplatin; D005472:Fluorouracil