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NF‐κ B‐dependent upregulation of ICAM‐1 by HPV16‐E6/E7 facilitates NK cell/target cell interaction
Author(s) -
Textor Sonja,
Accardi Rosita,
Havlova Tereza,
Hussain Ishraq,
Sylla Bakary S.,
Gissmann Lutz,
Cerwenka Adelheid
Publication year - 2010
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.25442
Subject(s) - downregulation and upregulation , microbiology and biotechnology , cell adhesion molecule , cell adhesion , receptor , biology , cell , intercellular adhesion molecule 1 , neural cell adhesion molecule , chemistry , biochemistry , gene
NK cell recognition of tumor cells is mediated by a delicate balance of signals received by MHC class I‐binding inhibitory NK cell receptors and activating NK cell receptors, which mainly bind to virus‐, stress‐ or tumor‐induced ligands. In addition, adhesion molecules such as the intercellular adhesion molecule‐1 (ICAM‐1) and its receptors, the lymphocyte function‐associated antigen‐1 (LFA‐1) and Mac‐1, are crucial for immune synapse formation and NK cell‐mediated killing. In this study, we show that expression of the adhesion molecule ICAM‐1 was rapidly induced by E6 and ‐E7 oncoproteins of HPV16, ‐18, ‐5 and ‐8, but not of HPV38 and ‐6 in primary human keratinocytes after retroviral transduction. ICAM‐1 was upregulated in E6E7‐expressing keratinocytes both at mRNA and protein levels. The observed ICAM‐1 upregulation in HPV16‐E6E7‐expressing keratinocytes was partially dependent on activation of the NF‐κB pathway. Importantly, the upregulated ICAM‐1 expression in HPV16‐E6E7‐expressing keratinocytes led to enhanced conjugate formation with NK cells. We previously showed that HPV16‐positive cervical carcinomas frequently express low levels of inhibitory NK cell ligands and high levels of activating NK cell ligands. Moreover, levels of the adhesion molecule ICAM‐1 are enhanced by HPV16‐E6/E7. Therefore, strategies that aim at harnessing NK cells might be beneficial for the treatment of cervical carcinoma.