Immunosuppression in renal cancer: Differential expression of signal transduction molecules in tumor-infiltrating, near-tumor tissue, and peripheral blood lymphocytes

Angela Riccobon, Roberta Gunelli, Ruggero Ridolfi, Franca De Paola, Emanuela Flamini, Massimo Fiori, Carlo Saltutti, Massimiliano Petrini, Laura Fiammenghi, Monica Stefanelli, Anna Maria Granato, Diego Ettore Cuzzocrea, Dino Amadori

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Abstract

Alterations in the expression of signal activation molecules, such as the T-cell receptor (TCR) ζ and ε 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 lmphocytes (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 ζ and ε 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 ζ chain and an almost complete absence of TCR ε chain and p56lck expression was observed in TIL (median values: 10% for ζ chain and 0% for ε 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 ζ and ε 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.

Original languageEnglish
Pages (from-to)871-877
Number of pages7
JournalCancer Investigation
Volume22
Issue number6
DOIs
Publication statusPublished - 2004

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Keywords

  • p56
  • Renal cell carcinoma
  • TCR ζ chain
  • Tumor-infiltrating lymphocytes (TIL)

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Riccobon, A., Gunelli, R., Ridolfi, R., De Paola, F., Flamini, E., Fiori, M., Saltutti, C., Petrini, M., Fiammenghi, L., Stefanelli, M., Granato, A. M., Cuzzocrea, D. E., & Amadori, D. (2004). Immunosuppression in renal cancer: Differential expression of signal transduction molecules in tumor-infiltrating, near-tumor tissue, and peripheral blood lymphocytes. Cancer Investigation, 22(6), 871-877. https://doi.org/10.1081/CNV-200039653