Interleukin 12-activated lymphocytes influence tumor genetic programs.

نویسندگان

  • F Cavallo
  • E Quaglino
  • L Cifaldi
  • E Di Carlo
  • A André
  • P Bernabei
  • P Musiani
  • G Forni
  • R A Calogero
چکیده

T-lymphocytes (LYs) from normal and IFN-gamma knockout mice were activated by anti-CD3 and anti-CD28 antibodies and cultured in inserts in the presence of interleukin (IL)-12 (IL-12-activated LYs) or not (activated LYs). Their ability to modulate the genetic programs of two tumor lines growing at the bottom of transwells was evaluated. cDNA gene expression array, reverse transcription-PCR, and protein expression showed that LPS, transcription termination factor 1, transforming growth factor, and fibroblast growth factor genes were up-modulated by factors other than IFN-gamma released by activated LYS: The high levels of IFN-gamma released by normal IL-12-activated LYs up-modulated the expression of STAT1, IRF-1, LMP2, LMP7, monokine induced by IFN-gamma, monocyte chemoattractant protein 1, and angiopoietin 2 genes but down-modulated the expression of vascular endothelial growth factor. PA28, IFN-inducible protein 10, inducible NO synthetase, and macrophage-inhibitory protein 2 genes were up-modulated by factors released only by IL-12-activated LYs apart from IFN-gamma. The opposite modulations of vascular endothelial growth factor expression and of angiopoietin 2, monokine induced by IFN-gamma, IFN-inducible protein 10, and inducible NO synthetase by IL-12-activated LYs fit in well with the inhibition of angiogenesis that characterizes the antitumor activity of IL-12. T-LYs thus modify a tumor's behavior so that it becomes a party to its own inhibition.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Interleukin 12-activated Lymphocytes Influence Tumor Genetic

T-lymphocytes (LYs) from normal and IFN-g knockout mice were activated by anti-CD3 and anti-CD28 antibodies and cultured in inserts in the presence of interleukin (IL)-12 (IL-12-activated LYs) or not (activated LYs). Their ability to modulate the genetic programs of two tumor lines growing at the bottom of transwells was evaluated. cDNA gene expression array, reverse transcription-PCR, and prot...

متن کامل

The Influence of Perforin Expression on the Sensitivity of LAK/NK Killing Against Various Tumor Target Cells

Background: Perforin is known to be important in cytolytic activity mediated by natural killer (NK) cells.   Objective: To study the relationship between the efficiency of NK and lymphokine-activated killer (LAK) cells activity, and the expression of perforin and HLA class I molecules.   Methods: LAK cells were generated by in vitro culturing of human peripheral blood lymphocytes (PBLs) in the ...

متن کامل

Lymphocyte-polarized DC1s

Activated lymphocytes secrete dendritic cell (DC)-activating cytokines including tumor necrosis factor α and interferon γ, and induce Type-1-polarized DCs (DC1s). Lymphocyte-polarized DC1s secrete high levels of biologically active interleukin-12 (IL-12p70) and CXCL10 and show enhanced CTL-inducing activity. Our data demonstrate the feasibility of using autologous lymphocytes to enhance the imm...

متن کامل

Lysis of neuroblastoma cell lines by human natural killer cells activated by interleukin-2 and interleukin-12.

Neuroblastoma is the most common extracranial, solid tumor in children. Despite intensive chemotherapy and bone marrow transplantation, the 5-year projected survival rate is 20% to 25%. In vitro studies have shown enhanced natural killer cell (NK) lysis of tumor cells after exposure of NK cells to interleukin-2 (IL-2). In vivo studies have demonstrated similar immunologic effects but have also ...

متن کامل

Anti-tumor effect of human lymphocytes and interleukin-2.

We studied the anti-tumor effect of control human lymphocytes and interleukin-2 (IL-2) activated lymphocytes (lymphokine activated killer cells, LAK-cells), on two different cell lines: SW742 human colon adenocarcinoma and K562 human myeloid leukaemia cell line. Our results indicate that IL-2 augment the anti-tumor activity of human lymphocytes and these LAK-cells lyse the tumor cells very effi...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Cancer research

دوره 61 8  شماره 

صفحات  -

تاریخ انتشار 2001