Our results demonstrate that the infiltration of colon cancer with DCs is related with tumor progression and patient prognosis, suggesting a central role for DCs in controlling local antitumor immunity.

The expression of TGF-beta1, its receptor TGFbetaRII, and signaling proteins Smad4 and Smad7 was observed in the majority of colorectal cancer specimens. Our results suggest that TGF-beta1 production by tumor cells may affect the tumor environment via suppression of tumor-infiltrating immune cells and probably contributes to tumor cells aggressiveness through autocrine activation of Smad signaling.

No abstract

Sarcoidosis is a disease of uncertainty in terms of its cause, presentation, and clinical course. The disease has a worldwide distribution and affects all ages, races, and both sex. Sarcoidosis of the skin may have an extremely heterogeneous clinical presentation, so that the definitions of 'great imitator' and 'clinical chameleon' have long been used. The factors that influence clinical picture and severity of the disease are probably linked to the etiopathogenesis of sarcoidosis, which continues to be shrouded in mystery. The current state of the art on the pathogenesis of sarcoidosis is that it is an immunological response in a genetically susceptible individual to an as-yet undefined antigenic stimulus. How exposure occurs in genetically predisposed patients is not completely clear, but the most likely explanation is that these agents or antigens are either inhaled into the lungs or enter through contact with the skin, as these are the common target organs that are constantly in contact with the environment. An autoimmune etiology of sarcoidosis could possibly occur through a process of molecular mimicry of infectious or other environmental antigens to host antigens. This could lead to a cross-mediated immune response and induction of autoimmune disease. This molecular mimicry may probably be responsible for the heterogeneous clinical presentations of the disease. Several investigations and studies have provided valuable evidence on the etiopathogenesis of sarcoidosis, which may lead to the future development of targeted and innovative treatment strategies. Nevertheless, we are still a long way from unravelling the underlying cause of this mysterious disease.

The aim of the study was to examine the main intrahepatic lymphocyte subpopulations, namely CD3(+) lymphocytes, natural killer (NK)-like T lymphocytes (NKT) expressing the CD3(+) CD56(+) phenotype, CD56(+) NK cells, CD4(+), and CD8(+) T cells in livers of patients with gastric and colorectal cancer with and without hepatic metastases. The proportion of each lymphocyte subset was determined in 34 patients with gastric or colorectal cancer (18 with and 16 without liver metastasis) by two-color flow cytometry after extraction of hepatic mononuclear cell fraction. The distribution of lymphocyte subpopulations in selected areas of liver metastases and adjacent liver tissue was evaluated using immunohistochemistry for CD4, CD8, and CD56. Flow cytometry analysis revealed a significant decrease in the proportion of CD3(+) CD56(+) cells in metastatic livers, but not in nonmetastatic livers (11.9 +/- 10.3 vs 24.2 +/- 13.6%, p = 0.02). The percentage of intrahepatic CD3(-)CD56(+) cells was also decreased in patients with metastases compared to those without (10.1 +/- 11.6 vs 16.6 +/- 8.9%, p = 0.039). Immunohistochemically, three types of lymphocytes (CD4(+), CD8(+), and CD56(+)) were present in the metastatic tissue, although the number of CD56(+) cells was almost twice lower. We found a low prevalence of tumor-infiltrating CD4(+), CD8(+), and CD56(+) cells in livers with multiple metastases, whereas in cases with solitary metastasis a higher degree of lymphocyte infiltration was observed. The number of CD3(-)CD56(+) and CD3(+) CD56(+) cells was decreased in metastatic livers compared to those unaffected by metastases. Therefore the prevalence of tumor-infiltrating lymphocytes seems to be related to the progression of metastatic liver disease. Depletion of hepatic innate lymphocytes may reveal susceptibility to metastatic liver disease and could be a reason for the escape of metastatic cells from the mechanisms of liver immune control.