Expression of TGF-beta 2 in human glioblastoma: a role in resistance to immune rejection?
Glioblastomas are among the most malignant tumours for which no curative treatment exists. A dysfunction of cellular immunity with decreased skin reactivity and lymphocyte blastogenesis has been described in patients with glioblastomas. In culture human glioblastoma cells release a factor termed glioblastoma-derived T cell suppressor factor (G-TsF) which inhibits the antigen-dependent growth of both helper and cytotoxic T cells. Purification and cloning indicated that G-TsF is a novel member of the TGF-beta family with a well-conserved mature sequence but less homology in the precursor segments. The factor was renamed TGF-beta 2. The two glioblastoma cell lines investigated expressed mRNAs for both G-TsF/TGF-beta 2 and TGF-beta 1 but only G-TsF/TGF-beta 2 protein was secreted. Neuroblastoma cells express only the mRNA for TGF-beta 1 but not the protein, nor the mRNA for G-TsF/TGF-beta 2. Recombinant G-TsF/TGF-beta 2 inhibits the generation of virus-specific cytotoxic T cells when injected into mice infected with lymphocytic choriomeningitis virus. Thus G-TsF/TGF-beta 2 might contribute to the impairment of tumour immune surveillance. Some T cell clones may escape the immunosuppressive effects of TGF-beta: ovalbumin-specific T helper cell lines that showed different degrees of susceptibility to TGF-beta contained clones which had lost receptor(s) for TGF-beta.
Fontana
A
A
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
Bodmer
S
S
Frei
K
K
Malipiero
U
U
Siepl
C
C
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D005909:Glioblastoma / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000209:etiology; D007157:Immunologic Surveillance / Q000187:drug effects; D007375:Interleukin-1 / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D009381:Neoplasms, Radiation-Induced / Q000473:pathology; D009474:Neurons / Q000166:cytology; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014615:Vaccinia / Q000276:immunology
D007375:Interleukin-1; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta