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Depressed monocyte polarization and clustering of dendritic cells in patients with head and neck cancer: In vitro restoration of this immunosuppression by thymic hormones

1993; Springer Science+Business Media; Volume: 36; Issue: 2 Linguagem: Inglês

10.1007/bf01754410

1432-0851

Maarten Tas, Peter J. Simons, Fons J. M. Balm, Hemmo A. Drexhage,

Antimicrobial Peptides and Activities

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. TheN-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-molecularmass 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.