Neuroblastoma in a 55-year-old patient: a case report.

BACKGROUND: Neuroblastomas account for 97% of all neuroblastic tumors and for approximately 15% of all pediatric cancer fatalities. However, in adults neuroblastoma is a very rare finding. CASE REPORT: Here, we present the case of a 55-year-old patient who was diagnosed with neuroblastoma stage IV one year after the false diagnosis of a non-secretory multiple myeloma. RESULTS: The patient received six cycles of a chemotherapy protocol with cisplatin, etoposide and vindesine alternating with vincristine, dacarbazine, ifosfamide and doxorubicin, but the response to treatment was insufficient (stable disease). CONCLUSION: The standard chemotherapy protocols used for children are not sufficient for adult patients. Different treatment approaches are needed to improve the prognosis of adult patients with neuroblastoma.

Prostate cancer lesions are surrounded by FOXP3+, PD-1+ and B7-H1+ lymphocyte clusters.

The immune response against prostate cancer seems to be inefficient although tumour cells show an over-expression of tumour-associated antigens suggesting that regulatory networks inhibit immune cell function locally. To address this proposition, lymphocytes within prostate cancer-inflicted tissue were analysed for the expression of markers associated with negative regulatory function and exhaustion. Prostate cancer, benign prostatic hyperplasia and healthy prostate tissues were investigated by immunohistology for CD25, FOXP3, PD-1 and B7-H1. We had previously documented that prostate cancer islets are surrounded by clustered accumulations of CD3+ lymphocytes, which lack perforin and interferon-gamma (IFNgamma) expression, thus are apparently quiescent. Here, we report that these clusters contain numerous CD25+ and FOXP3+ cells. These markers are associated with regulatory T cells, and their presence in lymphocyte clusters near prostate cancer regions indicates an environment with negative impact on immune response against cancer cells. Consistent with this hypothesis, cells expressing PD-1 and its ligand B7-H1, which are markers associated with exhaustion of lymphocyte function, were also detected in the lymphocyte clusters. Expression of molecules associated with inhibition and exhaustion of lymphocytes may reflect events contributing to ineffective immune responses against cancer cells.

Dominance of CD4+ lymphocytic infiltrates with disturbed effector cell characteristics in the tumor microenvironment of prostate carcinoma.

BACKGROUND: Prostate cancer is the most common cancer of men in the Western world. Despite the over-expression of tumor-associated antigens, like PSA or PSMA, immune activation is inefficient. The goal of this investigation was to assess in situ characteristics of prostate cancer-infiltrating lymphocytes and to determine their activation status and effector function. METHODS: We compared 17 carcinoma containing tissues, four benign prostatic hyperplasia tissues and eight healthy prostate tissues regarding lymphocyte subset composition, locoregional distribution, and functional status using immunohistological staining of cryopreserved tissues. For determination of lymphocyte subsets, serial sections were stained with CD3, CD4, and CD8 antibodies. Activation status and effector function were studied using CD69, interferon-gamma (IFN gamma), perforin, and CD3 zeta chain antibodies. T-cell-receptor repertoire (TCR) analysis was made to determine the complexity of infiltrating lymphocytes. RESULTS: CD3+, CD4+, and CD69+ T lymphocytes were prominent in tissues derived from patients with prostate carcinoma. CD8+ lymphocytes were significantly less than CD4+ lymphocytes. IFN gamma and perforin were downregulated on infiltrating lymphocytes compared to cells of healthy prostate tissue. Very few lymphocytes were detected within cancerous lesions whereas surrounding tissues showed extensive lymphocyte cluster formation. The TCR repertoire of infiltrating lymphocytes was broad and similar to that of healthy prostate tissue, giving no evidence for specific lymphocyte recruitment. CONCLUSIONS: In the prostate cancer microenvironment, CD4+ T lymphocytes dominated while CD8+ T cells were sparse. The lymphocytes exhibited signs of disturbed effector function. Consequently, the immune response against autologous tumor cells is likely to be inefficient in controlling tumor growth.

Presence of HSV-1 immediate early genes and clonally expanded T-cells with a memory effector phenotype in human trigeminal ganglia.

The latent persistence of herpes simplex virus type 1 (HSV-1) in human trigeminal ganglia (TG) is accompanied by a chronic CD8 T-cell infiltrate. The focus of the current work was to look for HSV-1 transcription activity as a potential trigger of the immune response and to characterize the immune cell infiltrates by this feature. We combined in situ hybridization, laser cutting microscopy, and single cell RT-PCR to demonstrate the expression of the HSV-1 immediate early (IE) genes ICP0 and ICP4 in human trigeminal neurons. Using CDR3 spectratyping, we showed that the infiltrating T-cells are clonally expanded, indicating an antigen-driven immune response. Moreover, the persisting CD8+ T-cells had features of the memory effector phenotype. The voltage-gated potassium channel Kv1.3, a marker of chronic activated memory effector cells, and the chemokines CCL5 and CXCL10 were expressed by a subpopulation of infiltrating cells. The corresponding chemokine receptors CCR5 and CXCR3 were co-expressed on virtually all CD8 T-cells. In addition, T-cells expressed granzymes and perforin. In contrast to animal models of HSV-1 latency, hardly any FoxP3-positive regulatory T-cells were detected in human TG. Thus, HSV-1 IE genes are expressed in human TG and the infiltrating T-cells bear several characteristics that suggest viral antigenic stimulation.