In vivo effects of thymostimulin treatment on monocyte polarization, dendritic cell clustering and serum p15E-like trans-membrane factors in operable head and neck squamous cell carcinoma patients.
Head and neck squamous cell carcinoma patients have been characterized by impairments in their cell-mediated immune system, particularly by decreased chemotactic function of monocytes and impairments in the function of the monocyte-derived dendritic cells (viz, a decreased capability to form cell "clusters"). These impairments are thought to be due to immunosuppressive factors of low molecular mass released by tumor, the so-called p15E-like factors. These suppressive effects of p15-like factors can be neutralized in vitro by thymic peptides, such as thymostimulin (TP1). In a randomized double-blind, placebo-controlled multicenter trial in the Netherlands, 41 patients with operable head and neck squamous cell carcinomas (HNSCC) were treated for 10 days prior to surgery with intramuscular TP1 in one of three dosages (0.5 mg/kg; 1.0 mg/kg or 2.0 mg/kg body weight) or treated with placebo. Assessment of monocyte chemotaxis, the capability of dendritic cells to form clusters and the presence of p15E-like low-molecular-mass factors (LMMFs) in serum was performed before TP1 treatment and on the day of surgery. Findings demonstrated that TP1 in a dose of 1.0 mg/kg and 2.0 mg/kg resulted in normalization of impaired monocyte chemotactic capability. Although the cluster capability of dendritic cells after TP1 treatment improved, values only reached statistical significance for the 0.5 mg/kg group. Serum p15E-like LMMF levels were not affected by TP1 treatment in any of the patient groups. Contrary to expectations we found no correlation between elevated immunosuppressive LMMFs and defective monocyte chemotaxis or cluster capability of dendritic cells. We conclude that treatment with TP1 can improve monocyte chemotaxis in HNSCC patients but an effect on the production of p15E-like factors by carcinoma cells could not be demonstrated.
Kerrebijn
J D
JD
Department of Otolaryngology Head and Neck Surgery, University Hospital Dijkzigt, Rotterdam, The Netherlands.
Simons
P J
PJ
Tas
M
M
Balm
A J
AJ
Drexhage
H A
HA
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D002449:Cell Aggregation / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000097:blood; D007369:Interferon Inducers / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects*; D009363:Neoplasm Proteins; D010919:Placebos; D012191:Retroviridae Proteins / Q000037:antagonists & inhibitors / Q000097:blood*; D013949:Thymus Extracts / Q000008:administration & dosage / Q000627:therapeutic use*; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors / Q000097:blood*
D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D007369:Interferon Inducers; D009363:Neoplasm Proteins; D010919:Placebos; D012191:Retroviridae Proteins; D013949:Thymus Extracts; D014759:Viral Envelope Proteins; C075727:retroviral p15E-related protein, human; C031407:thymostimulin