JAK3/STAT5/6 pathway alterations are associated with immune deviation in CD8 T cells in renal cell carcinoma patients.
Abstract
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.
Autore Pugliese
Tutti gli autori
-
GESUALDO L.;BATTAGLIA M.;DITONNO P.
Titolo volume/Rivista
Non Disponibile
Anno di pubblicazione
2010
ISSN
1110-7243
ISBN
Non Disponibile
Numero di citazioni Wos
Nessuna citazione
Ultimo Aggiornamento Citazioni
Non Disponibile
Numero di citazioni Scopus
14
Ultimo Aggiornamento Citazioni
Non Disponibile
Settori ERC
Non Disponibile
Codici ASJC
Non Disponibile
Condividi questo sito sui social