title: Immunotherapy of tumor with vaccine based on basic fibroblast growth factor-activated fibroblasts.
abstract: OBJECTIVE
  Cancer-associated fibroblasts play a key role in tumor progression. It is conceivable that the breaking of immune tolerance of "self-antigens" associated with tumor cells and tumor stromal is an attractive approach for tumor immunotherapy. To test this concept, we used basic fibroblast growth factor (bFGF) to activate normal fibroblasts and used these activated fibroblasts as one vaccine against tumor.
  
  
  METHODS
  Normal fibroblasts were treated with bFGF; their expressions of a-SMA and FAP were assessed by Western blot. We immunized mice with bFGF-activated fibroblasts. Auto-antibodies were assessed by flow cytometric and Western blot analysis. The deposition of auto-antibodies within the tumor tissues was assessed. The inhibition of proliferation of tumor cells and fibroblasts by purified immunoglobulins was investigated. The anti-tumor effects of purified immunoglobulins and lymphocytes of immunized mice were assessed.
  
  
  RESULTS
  The bFGF-activated fibroblasts were effective in affording protection from tumor onset, growth, and prolonging survival of tumor-bearing mice. The immunized sera exhibited positive staining for fibroblasts and tumor cells in FCAS and Western blot analysis. The purified immunoglobulins of immunized serum could inhibit the proliferation of tumor cells and fibroblasts in vitro and had the anti-tumor activity in vivo. There was the deposition of auto-antibodies within the tumor tissues. Adoptive transfer of lymphocytes of immunized mice revealed that cellular immune response is also involved. The anti-tumor activity could be abrogated by the depletion of CD4(+), CD8(+) T lymphocytes and NK cells.
  
  
  CONCLUSIONS
  In summary, bFGF-activated fibroblasts could induce an autoimmune response which was simultaneously against both cancer-associated fibroblasts and tumor cells in a cross-reaction.
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Medical School, West China Hospital, Sichuan University, Chengdu, 610017, Sichuan, China.
authors: Xiuying
authors: X
authors: Li
authors: Yongsheng
authors: Y
authors: Wang
authors: Yuwei
authors: Y
authors: Zhao
authors: Hengxiu
authors: H
authors: Yang
authors: Aiping
authors: A
authors: Tong
authors: Chengjian
authors: C
authors: Zhao
authors: Huashan
authors: H
authors: Shi
authors: Yang
authors: Y
authors: Li
authors: Zhenlin
authors: Z
authors: Wang
authors: Yuquan
authors: Y
authors: Wei
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005354:Fibrosarcoma / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014611:Vaccination
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D019496:Cancer Vaccines; D016222:Fibroblast Growth Factor 2