Comparison of retroviral p15E-related factors and interferon alpha in head and neck cancer.
Head and neck squamous cell carcinomas (HNscc) produce low-molecular-mass factors (low-M(r) factors, M(r) < or = 25,000), which are antigenically related to the immunosuppressive retroviral transmembrane 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 sequential and functional homology has been reported to exist between a bioactive fragment of interferon alpha (IFN alpha) and the putative immunosuppressive region of retroviral p15E (CKS-17). In this study we investigated (a) a possible functional and structural relationship between p15E and IFN alpha, and (b) the presence of and the relationship between p15E-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 leukaemia virus (p15E source). (c) Low-M(r) factors (n = 8-11) prepared from the sera of HNscc patients, which inhibit the monocyte chemotactic responsiveness, could be adsorbed by the anti-p15E antibodies as well as by the anti-IFN alpha antibodies. However, the abilities of the factors to adsorb to the two categories of antibodies (namely, anti-p15E and anti-IFN alpha) did not correlate. (d) Immunohistochemically we found IFN alpha-related epitopes, in almost all HNscc specimens studied (17/18), in locations distinctive from those of p15E-related factors. The anti-IFN alpha antibodies used in this study mainly reacted with basal epithelial cells close to the basal membrane, the prickle and granular cells of the squamous cell carcinomas. The anti-p15E antibodies mainly reacted with corneal layers, the granular and prickle cells, and did not react with basal epithelial cells. Our findings suggest that the immunosuppressive factors produced by HNscc cells are heterogeneous and p15E- and/or IFN alpha-related.
Simons
P J
PJ
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
Oostendorp
R A
RA
Tas
M P
MP
Drexhage
H A
HA
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology*; D006801:Humans; D007158:Immunologic Techniques; D007166:Immunosuppressive Agents / Q000737:chemistry*; D066298:In Vitro Techniques; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D012191:Retroviridae Proteins / Q000737:chemistry / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology*
D007166:Immunosuppressive Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins; C075727:retroviral p15E-related protein, human