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Although immunodeficiency is usually considered a prerequisite of oncogenesis, a detailed immune profile in cancer has not yet been described. Without such profiling, it is not surprising that there is a vast discrepancy in the responses of cancer patients to immunotherapy. Our results show that the integrity of the immune system deteriorates with cancer progression by displaying a trend toward decreasing levels of functional T cells, including CD4, naïve, and central memory T cells, and an expansion of hyporesponsive populations such as CD28− and CMV-specific T cells. One hundred and one patients constitute the study group for the observational study reported in this paper. Forty-eight patients with newly diagnosed stages III and IV and 53 patients with extensively treated stage IV disease. The costimulatory molecules CD27 and CD28 were downregulated in all patients. Among the proinflammatory cytokines (IL-6, TNF-α, IFN-γ), only IL-6 differed significantly among the groups, increasing as the cancer stage progressed. Plasma IL-7 did not differ among the participants. The relative deficits of naïve T cells in cancer patients may be associated with the downregulation of IL-7Rα expression rather than changes in the circulating levels of IL-7. The downregulation of IL-7Rα expression was shown to be associated with increased levels of intracellular CMV. The present study suggests that the immune impairment in patients with cancer is associated with multiple factors, such as the stage of cancer, consequence of CMV infection and impact of treatment. [ABSTRACT FROM AUTHOR]

Protein kinase (PK)C?is a critical regulator of mature T-cell activation and proliferation, being implicated in TCR-triggered nuclear factor (NF)-?B activation and providing important survival signals to leukemic T cells. We previously showed that overexpression of pTa/pre-TCR and constitutive activation of NF-?B characterize the T-cell leukemia/lymphoma developing in Notch3-IC transgenic mice. We report here that PKC?is a downstream target of Notch3 signaling and that its activation and membrane translocation require a functional pre-TCR in order to trigger NF-?B activation in thymocytes and lymphoma cells of transgenic mice. Furthermore, deletion of PKC?in Notch3-IC transgenic mice reduces the incidence of leukemia, correlating with decreased NF-?B activation. This paper therefore suggests that PKC?mediates the activation of NF-?B by pre-TCR in immature thymocytes and contributes to the development of Notch3-dependent T-cell lymphoma.Oncogene (2005) 24, 992-1000. doi:10.1038/sj.onc.1208302 Published online 13 December 2004 [ABSTRACT FROM AUTHOR]