Immature dendritic cells enhance antitumor effects
of hyperthermia

Reuters Health

NEW YORK (Reuters Health) - Injection of immature dendritic cells into tumors treated with hyperthermia enhances the antitumor effect, according to a report in the September 10th issue of the International Journal of Cancer.

Previous research has shown that hyperthermia induces antitumor immunity related to expression of heat shock proteins, which also activate dendritic cells, the authors explain.

Dr. Hiroyuki Honda, from Nagoya University in Japan, and colleagues investigated the feasibility of a novel therapy combining hyperthermia with magnetite cationic liposomes (to foster intracellular heating) and intratumoral injection of immature dendritic cells for malignant melanoma in a mouse model.
v Immature dendritic cells pulsed in vitro with heated tumor cells increased surface expression of various molecules, including the chemokine receptor CCR7, the authors report, indicating that heated tumor cells can induce dendritic cell maturation.

Melanoma tumors in mice treated with hyperthermia continued to grow progressively, the results indicate, but 2 of 10 similar mice treated with immature dendritic cells showed suppression of tumor growth.

Combination of hyperthermia with immature dendritic cell injection suppressed tumor growth, the researchers note, resulting in complete regression of 6 of 10 subcutaneous tumors.

Survival was prolonged slightly by dendritic cell treatment alone, the researchers note, but combination treatment with hyperthermia and immature dendritic cell injection significantly prolonged survival (p 0.05).

Combination therapy induced both cytotoxic T lymphocytes and natural killer cells, the report indicates, and all mice exhibiting complete regression of tumors rejected melanoma tumor cells injected subsequently.

"These results suggest that our hyperthermia system induced a vaccine-like effect caused by necrotic cell death via heat shock protein 70 expression in vivo and that its combination with immature dendritic cells was a potent therapeutic methodology," the investigators conclude.

"Based on these results," the authors add, "we believe that combination therapy of hyperthermia using magnetite cationic liposomes and intratumoral injection of immature dendritic cells is applicable to patients with advanced malignancies as a novel cancer therapy."

Int J Cancer 2005;116:624-633.