Optimization of hyperthermia and dendritic cell immunotherapy for squamous cell carcinoma

Abstract

Abstract. the aims of this study were to explore the feasibility of a novel combination therapy comprising hyperthermia (Ht) and dendritic cell (Dc) application for squamous cell carcinoma (scc), and to optimize the conditions of this therapy. In vitro, the correlation between maturation of Dcs by co-culture with sccVII cells and Ht was investigated. DCs did not mature in simple HT (43˚C for 30 min) with sccVII cells. on the other hand, Dc maturation occurred in additional mild HT (mHT: 41˚C for 30 min) with simple Ht. to assess whether additional mHt was effective, in vivo combined treatment was performed using tumor-bearing c3H/HeJ mice. A more suppressive effect of tumor growth was observed, and cytotoxic T cell infiltration was significantly increased by adding mHt compared to conventional only simple Ht with Dcs. these phenomena also occurred in non-treated contralateral tumors as well as treated ones. our data suggest that the combination of 43˚C preheated simple HT SCCVII tumors and additional 41˚C heat mHT promotes Dc maturation, resulting in suppression of tumor growth systemically and lifetime prolongation in mice. A three-step process of additional mHt after local Ht and intratumoral immature Dc (iDc) injection could be a more effective and novel method for the treatment of scc.

Hyperthermia Targeting the Tumor Microenvironment Facilitates Immune Checkpoint Inhibitors

“…Only when tumor cells and immature DCs are both under sequential hyperthermia treatment, can the immature DCs be effectively activated. This result suggests that DCs’ maturation not only depends on danger signals with HSPs but also on hyperthermia itself independently ( 61 ). Further studies proposed that fever-range hyperthermia promote DCs from a quiescent status to an activated status by promoting the metabolic reprogramming in them ( 62 , 63 ).…”

The Role of Hyperthermia in the Multidisciplinary Treatment of Malignant Tumors

“…23,24 For dendritic cells (DCs), which present antigens to adaptive immune cells, hyperthermia can enhance their proliferation, maturation, and antigen presentation. [25][26][27][28][29][30] Moreover, natural killer cells are activated and show elevated cytotoxicity and recruitment to tumor sites on heating, causing increased tumor cell recognition by natural killer cells. 31,32 Adaptive immune cells can also be targeted by heat.…”

Stressful Presentations: Mild Cold Stress in Laboratory Mice Influences Phenotype of Dendritic Cells in Naïve and Tumor-Bearing Mice

“…In vitro heating accelerates DC maturation as demonstrated by up-regulation of both CD86 and MHC class II (60, 61, 67). In vivo studies have also shown that up-regulation of both MHC class II and CD86 molecules on the surface of DCs from mice treated with whole body hyperthermia (61, 68). Additionally, hyperthermia in combination with other treatments including ionizing radiation (69), magnetic nanoparticles (70, 71), radiofrequency ablation (72) and vaccination (73, 74) results in enhanced DC function.…”