Tumor growth is allowed by its ability to escape immune system surveillance. An important role in determining tumor evasion from immune control might be played by tumor-infiltrating regulatory lymphocytes. This study was aimed at characterizing phenotype and function of CD8+CD28− T regulatory cells infiltrating human cancer. Lymphocytes infiltrating primitive tumor lesion and/or satellite lymph node from a series of 42 human cancers were phenotypically studied and functionally analyzed by suppressor assays. The unprecedented observation was made that CD8+CD28− T regulatory lymphocytes are almost constantly present and functional in human tumors, being able to inhibit both T cell proliferation and cytotoxicity. CD4+CD25+ T regulatory lymphocytes associate with CD8+CD28− T regulatory cells so that the immunosuppressive activity of tumor-infiltrating regulatory T cell subsets, altogether considered, may become predominant. The infiltration of regulatory T cells seems tumor related, being present in metastatic but not in metastasis-free satellite lymph nodes; it likely depends on both in situ generation (via cytokine production) and recruitment from the periphery (via chemokine secretion). Collectively, these results have pathogenic relevance and implication for immunotherapy of cancer.

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Mutations in the early growth response 2 (EGR2) gene are associated with some forms of Charcot‐Marie‐Tooth disease (CMT) and other demyelinating neuropathies. These mutations modify the EGR2 binding to specific DNA sequences suggesting a role in the transcriptional control of myelination‐specific genes. In this study we demonstrated that the D355V mutation, associated with a CMT case combining axonal and demyelinating abnormalities, reduces three times the affinity of EGR2 to its consensus sequence and ten times its affinity to a responsive element present in the human connexin 32 promoter. These findings could indicate that this EGR2 mutation leads to the development of CMT1 through the transcriptional deregulation of connexin 32. This research was partially supported by a MURST grant to FA, by a Ministero della Sanità grant to PM. Our laboratory is a member of the European Charcot‐Marie‐Tooth Consortium co‐ordinated by Prof. Christine Van Broeckhoven.