Depressed monocyte polarization and clustering of dendritic cells in patients with head and neck cancer: In vitro restoration of this immunosuppression by thymic hormones
Cancer Immunology, Immunotherapy: other biological response modifications , Volume 36 - Issue 2 p. 108- 114
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-molecularmass factor low-Mr factor; <25 kDa) sharing structural homology with p15E, the capsular protein of murine and feline leukemogenic retroviruses. The incubation of low-Mr 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-Mr factor (a mean of 42 versus 16% inhibition). This suppressive effect of patient low-Mr 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.
|Dendritic cells, Monocytes, p15E antigen, Squamous cell carcinoma, Thymostimulin, TP-1|
|Cancer Immunology, Immunotherapy: other biological response modifications|
|Organisation||Department of Immunology|
Tas, M.P.R, Simons, P.J, Balm, A.J.M, & Drexhage, H.A. (1993). Depressed monocyte polarization and clustering of dendritic cells in patients with head and neck cancer: In vitro restoration of this immunosuppression by thymic hormones. Cancer Immunology, Immunotherapy: other biological response modifications, 36(2), 108–114. doi:10.1007/BF01754410