title: Immunosuppression in renal cancer: differential expression of signal transduction molecules in tumor-infiltrating, near-tumor tissue, and peripheral blood lymphocytes.
abstract: Alterations in the expression of signal activation molecules, such as the T-cell receptor (TCR) zeta and epsilon chains and p56lck tyrosine kinase, are described in tumor-infiltrating lymphocytes (TIL). The aim of this study was to ascertain if such molecules were present in near-tumor-tissue lymphocytes (NTTL) and peripheral blood lymphocytes (PBL), as well as TIL, of renal cell carcinoma patients, to verify whether this tumor induces immunosuppression only locally or affects distant lymphocytes as well. Tissue from the tumor and from healthy nearby sites, as well as blood samples, were obtained from 27 consecutive patients who had undergone radical nephrectomy for renal cell carcinoma. Phenotype analysis and immunohistochemical staining of the TCR zeta and epsilon chains and p56lck were performed with standard techniques on TIL, NTTL, and PBL, and values were compared for each patient. Low expression of the TCR zeta chain and an almost complete absence of TCR epsilon chain and p56lck expression was observed in TIL (median values: 10% for zeta chain and 0% for epsilon and p56lck). In NTTL, these signal transduction molecules were expressed by a higher percentage of cells (60%, 50%, and 60%, respectively; p=0.000 vs. TIL), whereas PBL showed an almost normal expression of zeta and epsilon chains (80% and 90%, respectively; p=0.000 vs. TIL). Conversely, p56lck was detected in a greater proportion of NTTL than PBL (50% vs. 10%; p=0.001). The absence or the very low expression of signaling activation molecules in TIL compared with NTTL and PBL in renal cancer patients suggest that tumor-induced immunosuppression generally occurs or starts locally.
authors.affiliation: Department of Oncology, Pierantoni Hospital-AUSL, Forlì, Italy. a.riccobon@ausl.fo.it
authors.forename: Angela
authors.initials: A
authors.lastname: Riccobon
authors.forename: Roberta
authors.initials: R
authors.lastname: Gunelli
authors.forename: Ruggero
authors.initials: R
authors.lastname: Ridolfi
authors.forename: Franca
authors.initials: F
authors.lastname: De Paola
authors.forename: Emanuela
authors.initials: E
authors.lastname: Flamini
authors.forename: Massimo
authors.initials: M
authors.lastname: Fiori
authors.forename: Carlo
authors.initials: C
authors.lastname: Saltutti
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Petrini
authors.forename: Laura
authors.initials: L
authors.lastname: Fiammenghi
authors.forename: Monica
authors.initials: M
authors.lastname: Stefanelli
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Granato
authors.forename: Diego Ettore
authors.initials: DE
authors.lastname: Cuzzocrea
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007165:Immunosuppression Therapy; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology* / Q000502:physiology; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C061836:antigen T cell receptor, epsilon chain; C054979:antigen T cell receptor, zeta chain; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)