Retroviral p15E-related serum factors and recurrence of head and neck cancer

Abstract

Surgical removal of head and neck squamous cell carcinoma (HNSCC) restores the defective monocyte polarization found in patients with HNSCC. Since HNSCC contain p15E-like low molecular weight factors < 25 kD (LMWF) capable of suppressing N-formyl-methionyl-leucylphenylalanine (fMLP)-induced monocyte polarization, it is likely that HNSCC removal eradicates the production site of p15E-like factors. This report describes a prospective follow-up study on the levels of bioactive p15E-like serum factors for a period of 2 years in nine patients with HNSCC who had no recurrence and 11 patients with HNSCC who showed residual or recurrent disease after treatment. In the group of patients without recurrent disease p15E-like bioactivity gradually decreased and eventually became negative. In patients with recurrent/residual disease p15E-like bioactivity remained high or even became positive before or at the time of diagnosing tumour recurrence. This study strongly supports the concept that HNSCC tumours are the production site of p15E-like immuno-suppressive factors and indicates that serum p15E-like factors may be used for future studies on early serum markers for recurrent/residual disease developing in the first year after treatment.

Anti-Inflammatory and Vasoprotective Activity of a Retroviral-Derived Peptide, Homologous to Human Endogenous Retroviruses: Endothelial Cell Effects

“…We and others have previously reported association of retroviral p15E-related proteins with a variety of human neoplasms and certain normal tissues [1], [22], [66], [67], [68], [69]. In addition, human endogenous retroviruses (HERV) encoding for membrane proteins which contain the highly-conserved region from which MN10021 is derived, have also been identified in both normal and malignant human tissues [70]–[83].…”

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

“…The presence of immunosuppressive pl5E-like factors can be detected in the serum of HNSCC patients via a bioassay using healthy donor monocytes. In previous studies we showed that removal of a tumor often resulted in a postoperative decline of the level of these serum pl5E-like LMMFs [42], and restoration of monocyte chemotactic responsiveness [36]. We assumed that there was a direct effect on monocyte chemotaxis by immunosuppressive pl5E-like LMMFs produced by tumor and circulating in serum, since direct contact between monocytes and the serum pl5E-like factors seemed inevitable.…”

Cancer Associated Endogenous Retroviruses: Ideal Immune Targets for Adenovirus-Based Immunotherapy

“…Likewise, HERV-H's ISD was described to have the capacity to regulate immune escape [65]. Furthermore, decades old research unequivocally demonstrates that immunosuppressive peptides present in the serum of HNSCC patients cross-react with antibodies against mouse gamma retrovirus, like the murine antibodies against p15E [66][67][68]. Monoclonal antibodies against the immunosuppressive domain of the p15E protein demonstrated the important role of this region in the ENV protein as p15E depleted serum lost the immunosuppressive activity [69].…”