Migration and immunological reaction after the administration of αGalCer-pulsed antigen-presenting cells into the submucosa of patients with head and neck cancer.
BACKGROUND
Antigen-presenting cells (APCs) play a crucial role in the induction of immune responses. However, the optimal administration route of tumor-specific APCs for inducing effective immunological responses via cancer immunotherapy remains to be elucidated. Human NKT cells are known to have strong anti-tumor activities and are activated by the specific ligand, namely, α-galactosylceramide (αGalCer).


METHODS
Seventeen patients with head and neck squamous cell carcinoma (HNSCC) were enrolled in this study. Patients received an injection of αGalCer-pulsed APCs into the nasal, or the oral floor submucosa. Then total body image and single photon emission computed tomography (SPECT) images were examined. The immunological responses including the number of peripheral blood NKT cells, anti-tumor activities and the CD4(+) CD25(high) Foxp3(+) T cells (Tregs) induced following APCs were also compared.


RESULTS
APCs injected into the nasal submucosa quickly migrated to the lateral lymph nodes and those injected into the oral floor submucosa dominantly migrated to the submandibular nodes rather than the lateral lymph nodes. An increase in the absolute number of NKT cells and the IFN-γ producing cells was observed in peripheral blood after injection of the APCs into the nasal submucosa, however, these anti-tumor activities were not detected and the increased frequency of Treg cells were observed after administration into oral floor.


CONCLUSIONS
These results indicate that a different administration route of APCs has the potential to bring a different immunological reaction. The submucosal administration of αGalCer into the oral submucosa tends to induce immunological suppression.
Department of Otolaryngology and Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Motoyoshi
M
Kurosaki
Shigetoshi
S
Horiguchi
Kazuki
K
Yamasaki
Yoshitaka
Y
Uchida
Shinichiro
S
Motohashi
Toshinori
T
Nakayama
Akira
A
Sugimoto
Yoshitaka
Y
Okamoto
D058956:Administration, Mucosal; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000637:transplantation*; D015704:CD4 Antigens / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000628:therapy; D002465:Cell Movement; D005260:Female; D005699:Galactosylceramides / Q000276:immunology*; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000276:immunology*; D009297:Nasal Mucosa / Q000276:immunology*; D013194:Staining and Labeling; D016896:Treatment Outcome
D015704:CD4 Antigens; D005699:Galactosylceramides; D008024:Ligands; C493154:alpha-galactosylceramide