Thymostimulin enhancement of T-cell infiltration into head and neck squamous cell carcinoma.
BACKGROUND
Head and neck squamous cell carcinoma (HNSCC) produces immunosuppressive low-molecular-mass factors (LMMFs) responsible for defects in the cell-mediated immune system. These defects include impaired monocyte chemotaxis and an impaired capability of dendritic cells (DC) to form cellular clusters. It has been shown previously that the immunomodulating drug thymostimulin (TP1) restores these defects in vitro.


METHODS
An immunohistochemical study was performed on tumors of 18 patients with HNSCC who had preoperatively been treated with TP1 in one of three dosages (0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg body weight). Additionally, tumors of 4 patients who had been treated with a placebo and 12 patients who had not received any preoperative treatment were studied. A relative surface area of infiltration, meaning the percentage of stromal or epithelial tissue covered by infiltrating cells in histological sections, was calculated using an image analysis system (VIDAS RT) for CD3+ T-cells, CD14+/CD68+ monocytes/macrophages and L25+/CD1a+ dendritic cells for each tumor.


RESULTS
A highly significant, denser T-cell infiltration into the stromal tissue area of tumors of patients who had been treated with TP1 when compared with tumors of non-TP1-treated patients was observed for all three dosages. None of the other tumor-infiltrating cell types was affected by TP1. In addition, a correlation was found between the tumor T-cell infiltration and capability of DCs in the peripheral blood to form clusters with T-cells. No correlation existed between CD3+ T-cell numbers in peripheral blood and T-cell infiltration into the tumor; nor were monocyte chemotactic functions in peripheral blood correlated with tumor infiltration by monocytes or monocyte-derived macrophages and DCs.


CONCLUSIONS
Preoperative treatment of HNSCC patients with TP1 appears to strongly enhance tumor--T-cell infiltration. The number of tumor-infiltrating DCs was not affected by TP1, but a positive correlation between tumor--T-cell infiltration and DC clustering capability suggests that the functional status of DCs is important in improved cell-mediated immunity.
Kerrebijn
J D
JD
Department of Otolaryngology Head and Neck Surgery, University Hospital Dijkzigt, Rotterdam, The Netherlands.
Simons
P J
PJ
Balm
A J
AJ
Tas
M
M
Knegt
P P
PP
de Vries
N
N
Tan
I B
IB
Drexhage
H A
HA
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D015703:Antigens, CD; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000628:therapy; D002633:Chemotaxis / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007111:Immunity, Cellular; D008264:Macrophages / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D013949:Thymus Extracts / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D013949:Thymus Extracts; C031407:thymostimulin