DC immunotherapy is highly effective for the inhibition of tumor metastasis or recurrence, although it is not efficient for the eradication of established solid tumors.
Dendritic cell (DC)-based immunotherapy has not been as effective as expected in most solid tumors even in the murine model, particularly in renal cell carcinoma (RCC). Our investigation was initiated to identify what causes the limitations of DC-based immunotherapy in solid RCC. We have investigated immunosuppressive factors from tumors and their effects on DC migration, as well as cytotoxic T lymphocyte (CTL) response and lymphocyte infiltration into the tumor mass upon vaccination with mouse renal adenocarcinoma (Renca) cell lysate-pulsed bone marrow (Bm)-derived DC in tumor-bearing mice. We also investigated pulmonary metastasis- and tumor recurrence-inhibitory effects of DC-vaccination in the solid tumor-bearing mice. In these experiments, we found that the limitations of DC-based immunotherapy to solid RCC likely result from tumor-mediated TGF-beta hindrance of immune attack rather than insufficient immune induction by DC therapy. In fact, the CTL response induced by DC therapy was quite sufficient and functional for the inhibition of tumor recurrence after surgery or of tumor metastasis induced by additional tumor-challenge to the tumor-bearing mice. Taken together, our present results obtained in mouse model suggest the potential of DC immunotherapy in tumor patients for hindering or blocking disease progression by inhibition of tumor metastasis and/or tumor recurrence after surgery.
Lim
Dae-Seog
DS
Research Institute for DC Immunotherapy, CreaGene Inc, 2F Jungang Induspia V, 138-6 Sangdaewon-Dong, Jungwon-Gu, Seongnam-Si, Gyeonggi-Do, South Korea.
Kim
Jeong-Hwan
JH
Lee
Dong-Seong
DS
Yoon
Cheol-Hee
CH
Bae
Yong-Soo
YS
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000628:therapy*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D004195:Disease Models, Animal; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000628:therapy*; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000628:therapy*; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D019496:Cancer Vaccines; D053773:Transforming Growth Factor beta1