TY - JOUR
T1 - JAK3/STAT5/6 pathway alterations are associated with immune deviation in CD8+ T cells in renal cell carcinoma patients
AU - Ranieri, Elena
AU - Cavalcanti, Elisabetta
AU - Gigante, Margherita
AU - Mancini, Vito
AU - Battaglia, Michele
AU - Ditonno, Pasquale
AU - Capobianco, Carmela
AU - Cincione, Raffaele I.
AU - Selvaggi, Francesco P.
AU - Herr, Wolfgang
AU - Storkus, Walter J.
AU - Gesualdo, Loreto
PY - 2010
Y1 - 2010
N2 - To investigate the molecular mechanisms underlying altered T cell response in renal cell carcinoma (RCC) patients, we compared autologous and allogeneic CD8+ T cell responses against RCC line from RCC patients and their HLA-matched donors, using mixed lymphocyte/tumor cell cultures (MLTCs). In addition, we analyzed the expression of molecules associated with cell cycle regulation. Autologous MLTC responder CD8+ T cells showed cytotoxic activity against RCC cell lines; however the analysis of the distribution of CD8+ T-cell subsets revealed that allogenic counterparts mediate superior antitumor efficacy. In RCC patients, a decreased proliferative response to tumor, associated with defects in JAK3/STAT5/6 expression that led to increased p27KIP1 expression and alterations in the cell cycle, was observed. These data define a molecular pathway involved in cell cycle regulation that is associated with the dysfunction of tumor-specific CD8+ effector cells. If validated, this may define a therapeutic target in the setting of patients with RCC.
AB - To investigate the molecular mechanisms underlying altered T cell response in renal cell carcinoma (RCC) patients, we compared autologous and allogeneic CD8+ T cell responses against RCC line from RCC patients and their HLA-matched donors, using mixed lymphocyte/tumor cell cultures (MLTCs). In addition, we analyzed the expression of molecules associated with cell cycle regulation. Autologous MLTC responder CD8+ T cells showed cytotoxic activity against RCC cell lines; however the analysis of the distribution of CD8+ T-cell subsets revealed that allogenic counterparts mediate superior antitumor efficacy. In RCC patients, a decreased proliferative response to tumor, associated with defects in JAK3/STAT5/6 expression that led to increased p27KIP1 expression and alterations in the cell cycle, was observed. These data define a molecular pathway involved in cell cycle regulation that is associated with the dysfunction of tumor-specific CD8+ effector cells. If validated, this may define a therapeutic target in the setting of patients with RCC.
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U2 - 10.1155/2010/935764
DO - 10.1155/2010/935764
M3 - Article
C2 - 20339477
AN - SCOPUS:77951673112
SN - 1110-7243
VL - 2010
JO - Journal of Biomedicine and Biotechnology
JF - Journal of Biomedicine and Biotechnology
M1 - 935764
ER -