Cytokine-induced tumor immunogenicity: endogenous interleukin-1 alpha expressed by fibrosarcoma cells confers reduced tumorigenicity.
A direct correlation between the constitutive expression of IL-1 alpha and reduced tumorigenicity of fibrosarcomas was observed. This was established in fibrosarcoma cell lines which produce IL-1 alpha 'spontaneously', possibly as an aberration of oncogene-mediated transformation or upon IL-1 alpha gene transfer. In fibroblasts intracellular or membrane-associated IL-1 alpha is expressed, whereas the secreted form of the cytokine (IL-1 beta) is absent. Studies on the mechanisms of tumor regression of the IL-1 alpha-positive fibroblastoid cell lines indicated that IL-1 alpha potentiates the development of tumor cell-specific CTLs, which are of importance for tumor eradication. Thus, IL-1 alpha induces enhanced helper T cell activity which provides auxiliary signals for the growth/development of CTLs. Non-adaptive effector cells, activated locally by IL-1 alpha-expressing fibrosarcoma cells, also contribute to the eradication of IL-1 alpha-expressing fibrosarcomas. Local IL-1 alpha expression potentiated antigen presentation, by the malignant fibroblasts as well as by tissue-resident antigen-presenting cells, thus further potentiating anti-tumor immune responses. Mice, in which IL-1 alpha-producing tumors were regressed, developed an immune memory and rejected a challenge with an IL-1 non-producing violent tumor cell line. Endogenous IL-1 alpha activates a cytokine cascade (i.e., IL-6, CSF), produced by the malignant cells and possibly also by stromal cells. However, IL-1 alpha expression is essential for fibrosarcoma eradication, while other cytokines possibly amplify and sustain its action.(ABSTRACT TRUNCATED AT 250 WORDS)
Apte
R N
RN
Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel.
Douvdevani
A
A
Zoller
M
M
White
R M
RM
Dvorkin
T
T
Shimoni
N
N
Fima
E
E
Hacham
M
M
Huleihel
M
M
Benharroch
D
D
D016475:3T3 Cells; D000818:Animals; D002471:Cell Transformation, Neoplastic; D005354:Fibrosarcoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D007167:Immunotherapy; D007375:Interleukin-1 / Q000096:biosynthesis*; D051379:Mice; D008819:Mice, Nude; D012074:Remission Induction; D014162:Transfection
D007375:Interleukin-1