Ex vivo host response to gastrointestinal cancer cells presented by autologous dendritic cells.

BACKGROUND: Dendritic cells (DCs) capture apoptotic tumors and cross-present their antigens in the MHC class I and class II pathways for recognition by CD4+ and CD8+ T lymphocytes. Here we have tested the ability of fresh surgically resected colon and gastric cancer tumors to specifically activate host T lymphocytes when presented by autologous DCs. METHODS: DCs derived from adherent blood mononuclear cells of five patients, after a 7-day culture with GM-CSF and IL-4, were exposed to apoptotic autologous tumor (AAT) or apoptotic autologous peritumor normal (AAN) cells and cultured 24 h with monocyte-conditioned medium to achieve full DC maturation. Tumor-specific response was evaluated as single-cell cytokine release in an enzyme-linked immunospot (ELISPOT) and as cytotoxicity in a cold target inhibition (51)Cr-release assay. RESULTS: AAT-DCs induced specific IFN-gamma by T lymphocytes of two patients (rectal and gastric cancer), whereas in another two patients (rectal and gastric cancer) this response was depressed with a similar tumor-specific pattern and in one patient (rectal cancer) there was no response. Activation of IFN-gamma release was accompanied by tumor cytotoxicity and both responses were enhanced by IL-12, indicating the functional integrity of patients' lymphocytes. CONCLUSION: These data show that T-cell memory against rectal/gastric carcinoma antigens can be triggered by tumor-loaded autologous DCs. However, escape mechanisms may exist among tumors of the same histological origin that can inhibit this host response. A DC-based antitumor immunological monitoring assay with autologous tumor biopsies may allow patients to be screened to determine those who are suitable candidates for immune-based immunotherapy.

The steatocrit: a simple method for monitoring fat malabsorption in patients with cystic fibrosis.

Steatocrit was determined through microcentrifugation of fecal homogenate from 110 pediatric controls and 107 patients with cystic fibrosis (CF). For 74 CF patients, steatocrit was determined in the same fecal material collected to determine a fat balance. In controls, steatocrit value was 0.7 +/- 1.0%, which was significantly lower than values found in CF patients with a coefficient of fat excretion less than 10% of intake (1.7 +/- 1.2%). Significantly increased values were found in CF patients with a coefficient of fat excretion ranging between 10 and 25% of intake (4.7 +/- 1.7%) and in those whose coefficient of fat excretion was greater than 25% of intake (11.3 +/- 4.3%). In the 74 CF patients, steatocrit was directly correlated to the coefficient of fat excretion (r = 0.93; P less than 0.001). We performed steatocrit several times in the course of the 1st year of life in 33 infants with CF diagnosed by means of CF screening. Values obtained at the time of diagnosis, before starting enzymatic therapy, were relatively high; they showed a progressive decrease when, using steatocrit as a guide, the dose of pancreatic enzymes had been increased. The normalization of steatocrit values was accompanied by a better growth rate in the majority of these infants, confirming the importance of an optimal early correction of pancreatic insufficiency. We propose that this simple semiquantitative test can be usefully performed for the frequent monitoring of fat absorption and for checking the response to enzymatic therapy in patients with CF.