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Abrogated NK‐cell lysis of human papillomavirus (HPV)‐16‐bearing keratinocytes in patients with pre‐cancerous and cancerous HPV‐induced anogenital lesions
Author(s) -
Malejczyk Jacek,
Majewski Slawomir,
Jablonska Stefania,
Rogozinski Tomasz T.,
Orth Gerard
Publication year - 1989
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910430206
Subject(s) - condyloma acuminatum , peripheral blood mononuclear cell , cell , pathology , monoclonal antibody , medicine , cancer research , antibody , human papillomavirus , immunology , biology , in vitro , biochemistry , genetics
Natural‐cell‐mediated cytotoxicity against K‐562 erythroleukemic cells and human papillomavirus (HPV)‐16 harboring Sk‐v keratinocytes was tested in 38 age‐ and sex‐matched healthy volunteers and in patients with HPV‐induced benign and malignant anogenital lesions: 9 persons with HPV‐16‐induced bowenoid papulosis (BP), 8 with anogenital carcinomas (5 with HPV‐16‐ or 33‐associated squamous‐cell carcinomas of Bowen's type and 3 with HPV‐6‐associated Buschke‐Loewenstein verrucous carcinomas) and 12 with HPV‐6‐induced condylomata acuminata. Both K‐562 and Sk‐v cells were killed by a non‐adherent CD16 + subset of PBMC as revealed by cell fractionation on the basis of their adherence to plastic and by treatment with Leu‐IIb monoclonal antibody (MAb) and complement. “Cold” target competitive assays demonstrated that both cell types inhibited lysis of labelled Sk‐v cells. In patients with BP and anogenital carcinomas induced by HPV‐16 or 33, there was a significant (at least at p < 0.01) decrease of Sk‐v cell lysis as compared with the healthy control group. Anti‐K‐562 activity was not affected. In patients with anogenital carcinomas the degree of Sk‐v lysis was decreased in proportion to the duration of lesions (correlation coefficient–r = ‐0.79). Neither anti‐K‐562 nor anti‐Sk‐v cytotoxicities were significantly affected in patients with condylomata and with HPV‐6 associated verrucous carcinomas. Short‐term (3 hr) pre‐incubation of normal PBMC with sera from patients with BP and HPV‐16‐associated anogenital carcinomas resulted in significant inhibition of their ability to lyse Sk‐v cells. Lysis of K‐562 cells remained unaffected. In patients with carcinomas, the suppressive effect of sera was associated with a lowering of the ability of their PBMC to lyse Sk‐v cells (r = ‐0.79). In patients with longer tumor persistence, the suppressive effect of serum was proportionally higher (r = 0.86).