Classical Hodgkin Lymphoma (cHL) is morphologically characterized by a small number of tumour cells, Hodgkin and Reed-Sternberg (HRS) cells, surrounded by numerous tumour-infiltrating lymphocytes (TIL). The functional role of these TIL is still controversial. While generally considered to represent an anti-tumour immune response, TIL in cHL might result from the profoundly deregulated immunity of cHL patients. Eighty-seven cases of cHL were available to evaluate the prognostical significance of tumour-infiltrating cytotoxic T lymphocytes (CTL), T helper 1 (Th1) cells, T helper 2 (Th2) cells and regulatory T cells (Treg). We confirm that in cHL the microenvironment is dominated by Th2 cells and Treg and show that large numbers of Th2 cells are associated with significantly improved disease-free survival ( p ¼ 0.021) and event-free survival ( p ¼ 0.012). Furthermore, a high ratio of Treg over Th2 cells resulted in a significantly shortened disease-free survival ( p ¼ 0.025). These observations suggest that Treg may exert inhibitory effects on antitumour immune responses mediated through Th2 cells and that Th2 cells may be more important for effective anti-tumour immunity than anticipated.

Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes in antigen-dependent B-cell maturation. SHM is not restricted to immunoglobulin gene loci, raising the possibility of a function for AID in other cell types. In this study, it is shown that AID is expressed in spermatocytes in the human testis. AID was mostly cytoplasmic but nuclear AID was also observed in a proportion of cells, in keeping with the DNA deamination model of AID function. Intratubular germ cell neoplasia unclassified (IGCNU), the precursor lesion of testicular cancers, was AID-negative. Seminomas also lacked AID expression. Nuclear and cytoplasmic AID expression was observed in three of 32 mixed non-seminomatous germ cell tumours. The results provide evidence for a physiological role for AID outside the immune system. AID expression in spermatocytes points to a role in meiosis. It remains uncertain whether AID may also contribute to the genetic aberrations characteristically found in testicular germ cell tumours. The consistent absence of detectable AID expression in atypical spermatogonia of IGCNU and its rare expression in germ cell tumours suggest that continued expression of AID is not involved in the pathogenesis of germ cell tumours.

Epstein-Barr virus (EBV)-associated undifferentiated nasopharyngeal carcinoma (NPC) is characterized by a prominent nonneoplastic lymphoid stroma. The functional role of these inflammatory cells and the mechanism of their recruitment are not fully understood. In B-cells, the EBV-encoded latent membrane protein 1 (LMP1) can induce the expression of chemokines in an NF-jB dependent manner. We now show that LMP1 can induce the expression of RANTES and MCP-1 in an epithelial cell line, and that this effect is partially reversible by an inhibitor of NF-jB. Since tumor cells of virtually all NPCs show CD40 expression while many cases are LMP1-negative at the protein level, we also investigated the effect of CD40 signaling and demonstrate that CD40 stimulation can transiently induce RANTES and MCP-1 expression in LMP1-negative epithelial cells. In in situ hybridization only rare tumor cells showed expression of these chemokines unrelated to LMP1 expression, a pattern consistent with transient induction through CD40 signaling. Since RANTES and MCP-1 were also detected in the neoplastic cells of oral squamous cell carcinomas lacking a lymphoid stroma it remains uncertain to what extent these CC chemokines contribute to the attraction of inflammatory cells into the NPC microenvironment. ' 2007 Wiley-Liss, Inc.

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