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 Immunol Immunother. 1993;36(2):108-14. doi: 10.1007/BF01754410.

Abstract

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.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Adult
  • Aged
  • Carcinoma, Squamous Cell / immunology*
  • Chemotaxis, Leukocyte / drug effects*
  • Dendritic Cells / drug effects*
  • Dendritic Cells / physiology
  • Female
  • Head and Neck Neoplasms / immunology*
  • Humans
  • Immune Tolerance / drug effects*
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / immunology*
  • Thymus Extracts / pharmacology*

Substances

  • Adjuvants, Immunologic
  • Thymus Extracts
  • thymostimulin