Artificial cytokine storm combined with hyperthermia induces significant anti-tumor effect in mice inoculated with lewis lung carcinoma and B16 melanoma cells.

In cancer immunotherapies combined with hyperthermia, one or two cytokines have been tested to augment the anti-tumor effect. However, the therapies have not shown sufficient improvement. The aim of this study is to find a new potent tumor immunotherapy in order to augment antitumor effect of hyperthermia by the cytokine cocktails in vivo. We used a combination therapy of local hyperthermia (LH) and various cytokine cocktails composed of IFNs (IFN-alpha, -beta, and -gamma), Thl cytokines (IL-2, -12, -15, and -18), a Th2 cytokine (IL-4), inflammatory cytokines (IL-lalpha and TNF-alpha), and dendritic cell-inducible cytokines (IL-3 and GM-CSF). These cytokines in a proper combination augmented the anti-tumor effect of LH and prolonged survival time in Lewis lung carcinoma or B16 melanoma significantly. Moreover, the 12-cytokine cocktail suppressed B 16 metastasis to the lung and lymph nodes, and complete regression of the tumors without regrowth occurred in 3 of 5 mice. In the cured three B16 mice, there was hyperplasia of lymphatic organs with many CD3-positive T lymphocytes. The most effective cytokine combination should be able to augment the anti-tumor effect of other therapies besides hyperthermia that induce the necrosis of tumor cells.

The intraductal component of breast cancer is poorly responsive to neo-adjuvant chemotherapy.

Neo-adjuvant chemotherapy has been used for locally advanced breast cancers. With special attention to the proportion of intraductal component, we pathologically studied 25 patients that underwent neo-adjuvant chemotherapy via intra-arterial infusion or intravenous injection. In general, neo-adjuvant chemotherapy had a favorable effect on tumor reduction. The effectiveness varies depending on the predominance of intraductal component. The cases with a high proportion of intraductal component had lower response to the chemotherapies. The larger number of cancer cells remained within the mammary ducts. The residual cancer cells conserved proliferative activity. Intraductal component is poorly responsive to neoadjuvant chemotherapy.