COMPARISON OF RETROVIRAL P15E-RELATED FACTORS AND INTERFERON-ALPHA INHEAD AND NECK-CANCER

Head and neck squamous cell carcinomas (HNscc) produce low-molecular-m ass factors, (low-M(r) factors, M(r) less than or equal to 25,000), wh ich are antigenically related to the immunosuppressive retroviral tran smembrane envelope protein p15E. These P15E-related tumour factors are thought to be responsible for some immunological impairments found in these patients (particularly the defective monocyte chemotaxis). A se quential and functional homology has been reported to exist between a bioactive fragment of interferon alpha (IFN alpha) and the putative im munosuppressive region of retroviral p15E (CKS-17). In this study we i nvestigated (a) a possible functional and structural relationship betw een p15E and IFN alpha, and (b) the presence of and the relationship b etween pl5E-related low-M(r) factors and IFN alpha in HNscc patients. We report the following results. (a) Recombinant human (rhu) IFN alpha was able to inhibit monocyte chemotaxis. (b) The anti-p15E antibodies crossreacted with rhuIFN alpha in a dot-blot technique; however, the anti-IFN alpha antibodies did not crossreact with disrupted murine leu kaemia virus (p15E source). (c) Low-Mr factors (n = 8-11) prepared fro m the sera of HNscc patients, which inhibit the monocyte chemotactic r esponsiveness, could be adsorbed by the anti-p15E antibodies as well a s by the anti-IFN alpha antibodies. However, the abilities bf the fact ors to adsorb to the two categories of antibodies (namely, anti-p15E a nd anti-IFN alpha) did not correlate. (d) Immunohistochemically we fou nd IFN alpha-related epitopes, in almost all HNscc specimens studied ( 17/18), in locations distinctive from those of pl5E-related factors. T he anti-IFN alpha antibodies used in this study mainly reacted with ba sal epithelial cells close to the basal membrane, the prickle and gran ular cells of the squamous cell carcinomas. The anti-p15E antibodies m ainly reacted with corneal layers, the granular and prickle cells, and did not react with Head and neck squamous cell carcinomas produce low -molecular-mass factors (low-Mr basal epithelial cells. Our findings s uggest that the immunosuppressive factors produced by HNscc cells are heterogeneous and p15E- and/or IFN alpha-related.