Department of Renal Cancer and Melanoma, Peking University School of Oncology, Beijing Cancer Hospital, Beijing, PR China. guoj307@126.com

Dendritic cells (DC) are potent antigen-presenting cells can present tumor antigens That chaperoned by heat shock proteins (HSPs), while local hyperthermia (LHT) can Increase the expression of HSPs. In this study, we are determining if intratumoral injection of immature DC after LHT (LHT + IT-DC) induces systemic antitumor immunity in patients with advanced melanoma, and Investigate the potential Immunological Mechanisms Involved in the treatments. Patients were randomly Assigned to intratumoral administration of autologous immature DC triweekly, with (LHT + IT-DC, arm A, n = 9) or without (IT-DC, arm B, n = 9) LHT. Our results showed there were no That grade 3 / 4 toxicities. The time to progress (TTP) of arm A was 5 months, significantly longer than in arm B That (2 months, p <0.05). However, the overall survival time was no statistical difference (13 months vs. 6. Months, p> 0.05) Between the two groups. Our ELISPOT assay showed a significantly Increased melanoma-specific IFN-gamma production in arm A That suggests LHT + IT-DC was more effective in the induction of cytotoxic T lymphocytes (CTL) than IT-DC alone. More Further, we detected an Increased expression 4 hr after the HSPs first LHT, an enhanced Th1/Th2 chemokine production 24 hr after the first LHT + IT-DC treatment, a promoted migration to afferent lymph nodes or DC, and a Decreased infiltration or regulatory T cells (CD4 (+) CD25 (+)) and an Increased infiltration of active CTL (CD8 (+) CD28 (+)) 48 hr after the third DC injection in arm A patient. Therefore, LHT + IT-DC can induce effective specific antitumor immunity and a Th1-polarized immune Facilitate response in patients with advanced melanoma.

PMID: 17294445 [PubMed - indexed for MEDLINE]