The expression and activity of MMPs are increased in residual tumor tissues after the termination of immunotherapy.
To investigate the invasive ability of the residual tumor cells after immunotherapy and explore the feasible approach suppressing the invasion, mice were inoculated with B16 cells, and then treated by gene therapy with p4-1BBL/psPD-1 or IFN-gamma. The production and activities of MMP-9 and MMP-2 in residual tumor tissues were analyzed with gelatin zymography 1 day and 7 days after the termination of the immunotherapy. The production of MMP-9 and MMP-2 by B16 cells treated with IFN-gamma was also analyzed. IFN-gamma-treated B16 cells were inoculated to mice via subcutaneous injection. The invasion of tumor to muscular tissue was analyzed. Gene therapy with CH50 was used to suppress the invasive growth of tumor. The results showed that the expression and the activities of MMP-9 and MMP-2 were significantly increased 7 days after the end of immunotherapy. The response of tumor cells to ECM molecules was intensified after the removal of IFN-gamma, resulting in significant increase of both the production and activities of MMP-9 and MMP-2, and the increased invasion of tumor. Gene therapy with CH50 effectively suppressed the invasive growth of tumor. It is concluded that the termination of immunotherapy may result in a higher metastatic potential of residual tumor cells. Suppressing tumor invasion by suitable treatment will improve the efficacy of immunotherapy.
Xiong
Ting
T
Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Peng
Huimin
H
Chen
Guoxi
G
Yuan
Ye
Y
D000818:Animals; D003131:Combined Modality Therapy; D005260:Female; D005353:Fibronectins / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods; D007167:Immunotherapy / Q000009:adverse effects*; D007371:Interferon-gamma / Q000627:therapeutic use; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000627:therapeutic use
C478562:CH50 recombinant polypeptide; D005353:Fibronectins; D011994:Recombinant Proteins; D007371:Interferon-gamma; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse