Depressed monocyte polarization and clustering of dendritic cells in patients with head and neck cancer: in vitro restoration of this immunosuppression by thymic hormones.
The in vitro restoring effects of a thymic hormone preparation, TP-1, on defective monocyte and dendritic cell function in patients with head and neck squamous cell carcinoma (HNSCC) have been examined. The N-formylmethionyl-leucyl-phenylalanine (fMLF)-induced polarization of monocytes isolated from the peripheral blood was significantly lower (a mean of 19%) than the polarization of monocytes isolated from healthy controls (a mean of 33%). After the in vitro addition of TP-1 this defective polarization was improved to the normal value of 33% polarized monocytes. The capability of dendritic cells prepared from the blood to form cellular clusters with allogeneic cells was impaired in 26/44 patients. In vitro addition of TP-1 again had restoring effects. The original defective dendritic cell clustering of 97 clusters/six microscopic fields (mean) was improved to a value of 121 clusters. The defects in monocyte polarization and clustering of dendritic cells could be ascribed to the presence in serum of a tumor-derived low-molecular-mass factor low-M(r) factor; < 25 kDa) sharing structural homology with p15E, the capsular protein of murine and feline leukemogenic retroviruses. The incubation of low-M(r) factor from the serum of HNSCC patients with healthy donor monocytes resulted in a significantly higher inhibition of fMLF-induced monocyte polarization than did incubation with control low-M(r) factor (a mean of 42 versus 16% inhibition). This suppressive effect of patient low-M(r) factor was abrogated with a mixture of two monoclonal antibodies against p15E as well as with TP-1. The observations here reported on the in vitro effects of TP-1 on depressed monocyte and dendritic cell function in HNSCC have provided one of the rationales for a TP-1 therapeutic pilot trial recently started in HNSCC patients.
Tas
M P
MP
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
Simons
P J
PJ
Balm
F J
FJ
Drexhage
H A
HA
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D013949:Thymus Extracts / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D013949:Thymus Extracts; C031407:thymostimulin