The effect of stress on efficacy of dendritic cell therapy for esophageal squamous cell carcinoma.
ABSTRACT
Background: Recently, abscopal effect, by which systemic anti-tumor effect by local radiation therapy (RT) was elicited, has been reported. This phenomenon was thought to be mediated by stress protein gp96, a key molecule in antigen-presenting. We tested the enhancement of dendritic cell (DC) therapy by various stress, such as radiation or modulated electro-hyperthermia (mEHT) in DC therapy for squamous cell carcinoma (SCC).
Methods: Mouse SCC cells, SCCVII, were inoculated into the left femur (primary tumor) of C3H/He mice subcutaneously, and also similarly inoculated into non-treated chest subcutaneous tissue (secondary tumor). Only the primary tumor was exposed to 4 or 10 Gy of RT or 5-10 watts of mEHT. Then DCs was injected only into the primary tumor. Following that, tumor volumes of the primary and secondary tumor were measured. Next, the population of immune-related T-cells in tumor-draining lymph nodes (TDLN) and gp96 expression in the primary tumor were evaluated.
Results: With intratumoral injection of DCs and RT, primary tumor growth was markedly suppressed. Furthermore, secondary tumor growth was also suppressed. On the other hand, the combination of DCs and mEHT could inhibit tumor growth at both the primary and the secondary tumor. As for the population of T-cells, the population of CD3+, CD 4+ and CD 8+T-cells in the TDLN was markedly elevated and that of FoxP3 was reduced my mEHT. Gp96 expression, a stress protein, was strongly enhanced after RT and mEHT.
Conclusions: Stress, such as RT or hyperthermia can enhance the efficacy of DC therapy and can induce a strong antitumor effect by stimulating the expression of stress protein, gp96. These combination therapies can be a strong systemic immunotherapy for esophageal SCC.