Classical Hodgkin's lymphoma (cHL) is characterized by the presence of an abundant reactive infiltrate, lacking effective cytotoxic responses. Especially in Epstein-Barr virus (EBV)-negative cHL, the neoplastic Hodgkin-Reed-Sternberg (HRS) cells have lost protein expression of major histocompatibility complex (MHC) class I, enabling escape from cytotoxic T lymphocyte (CTL) responses. However, downregulation of MHC class I generally induces natural killer (NK) cell activation. The paucity of NK cells in the reactive infiltrate of cHL and the systemic NK cell deficiency observed in cHL patients led us to investigate the expression of human leukocyte antigen (HLA)-G, which is known to inhibit NK-cell- and CTL-mediated cytotoxicity. By immunohistochemistry, HLA-G protein was expressed by HRS cells in 54% (95/175) of cHL cases. This expression was associated with absence of MHC class I on the cell surface of HRS cells (P < 0.001) and EBV-negative status (P < 0.001). Previously, genetic markers located in the proximity of the HLA-A and HLA-G genes had been shown to be associated with susceptibility to EBV-positive cHL. In the present study, these markers associated with MHC class I protein expression but not with presence of HLA-G. Our results suggest that induction of HLA-G protein expression in HRS cells contributes to the modulation of immune responses observed in cHL.

Since Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL) generally have immuno-1-4 Immunohistochemical analysis of the neoplastic cells of CHL has revealed an immunophenotype that is very specific, but highly unusual for a B-cell-derived tumor. The so-called Hodgkin and Reed-Sternberg (HRS) cells typically express CD30 and CD15, have inconsistent expression of CD20 and CD79a, and typically lack J-chain and immunoglobulins. 5,6 The neoplastic cells of NLPHL, the so-called lymphocytic and histiocytic (L&H)-type HRS cells, do express classical B-cell markers like CD20, CD79a, and J-chain 7 but lack CD30 and CD15.

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