Cervical cancer cells induce apoptosis of cytotoxic T lymphocytes.
The goal of immunotherapy is to eliminate tumors by generating tumor-specific cytotoxic T lymphocytes (CTLs) in patients or by adoptively transferring ex vivo-activated CTLs into patients. Clinical trials have shown that tumor-specific CTLs often disappear before tumors are completely eliminated. In this study, the authors show that CTLs specific for cervical tumor cells undergo apoptosis after they are co-cultured with cervical tumor cells. The established cervical tumor cell lines and cervical cancer tissues express CD95 (Fas/Apo-1) ligand. The tumor cell-induced T-cell apoptosis can be blocked by an inhibitory anti-CD95 (APO-1/Fas) antibody, indicating that tumor cells induce apoptosis of CTLs through CD95-CD95 ligand interaction. Addition of interleukin-2 (IL-2) and IL-7 into the culture rescues the CTL from tumor cell-induced apoptosis. The rescued T cells retain their full antitumor cytotoxicity. These data suggest that human cervical tumor cells might actively down-regulate a cellular immune response by inducing apoptosis of specific T cells during immunotherapy. Local use of IL-2 and IL-7 as adjuvants may promote survival of the CTL and, thus, enhance the efficacy of immunotherapy.
Contreras
D N
DN
Department of Microbiology, Stritch School of Medicine, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Krammer
P H
PH
Potkul
R K
RK
Bu
P
P
Rossi
J L
JL
Kaufmann
A M
AM
Gissmann
L
L
Qiao
L
L
D017209:Apoptosis / Q000276:immunology*; D018920:Coculture Techniques; D053222:Fas Ligand Protein; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D015851:Interleukin-7 / Q000276:immunology / Q000494:pharmacology; D019169:Jurkat Cells; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007376:Interleukin-2; D015851:Interleukin-7; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor