Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer T-cell interactions for individual patients and understand determinants of responsiveness are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses to epithelial cancers in a personalized manner. We demonstrate that co-cultures of autologous tumor organoids and peripheral blood lymphocytes can be used to enrich tumor-reactive T cells from peripheral blood of patients with mismatch repair-deficient colorectal cancer and non-small-cell lung cancer. Furthermore, we demonstrate that these T cells can be used to assess the efficiency of killing of matched tumor organoids. This platform provides an unbiased strategy for the isolation of tumor-reactive T cells and provides a means by which to assess the sensitivity of tumor cells to T cell-mediated attack at the level of the individual patient.

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Purpose To prospectively compare the diagnostic accuracy of controlled attenuation parameter (CAP) obtained with transient elastography and proton density fat fraction (PDFF) obtained with proton magnetic resonance (MR) spectroscopy with results of liver biopsy in a cohort of adult patients suspected of having nonalcoholic fatty liver disease (NAFLD). Materials and Methods The institutional review board approved this study. Informed consent was obtained from all patients. The authors evaluated 55 patients suspected of having NAFLD (40 men, 15 women). Patients had a median age of 52.3 years (interquartile range [IQR], 43.7-57.6 years) and a median body mass index of 27.8 kg/m (IQR, 26.0-33.1 kg/m). CAP and PDFF measurements were obtained on the same day, within 27 days of biopsy (IQR, 7-44 days). CAP and PDFF were compared between steatosis grades by using the Jonckheere-Terpstra test. Diagnostic accuracies of CAP and PDFF for grading steatosis were assessed with receiver operating characteristic (ROC) analysis. Within-weeks reproducibility (CAP and PDFF) and within-session repeatability were assessed with linear regression analyses, intraclass correlation coefficients, and coefficients of variation. Results Steatosis grades at liver biopsy were distributed as follows: S0, five patients; S1, 24 patients; S2, 17 patients; and S3, nine patients. Both PDFF and CAP helped detect histologically proven steatosis (≥S1), but PDFF showed better diagnostic accuracy than CAP in terms of the area under the ROC curve (0.99 vs 0.77, respectively; P = .0334). PDFF, but not CAP, enabled the grading of steatosis (P < .0001). For within-weeks reproducibility, the intraclass correlation coefficient with PDFF was higher than that with CAP (0.95 vs 0.65, respectively; P = .0015); coefficients of variation were similar (19% vs 11%, P = .55). Within-session repeatability of CAP was good, with a coefficient of variation of 4.5%. Conclusion MR spectroscopy-derived PDFF is superior to CAP in detecting and grading liver steatosis in human NAFLD. RSNA, 2017 Online supplemental material is available for this article.

Background: Higher circulating insulin-like growth factor I (IGF-I) concentrations have been related to a greater risk of cancer. Lycopene intake is inversely associated with cancer risk, and experimental studies have shown that it may affect the IGF system, possibly through an effect on IGF-binding proteins (IGFBPs). Objective: The objective of our study was to investigate the effect of an 8-wk supplementation with tomato-derived lycopene (30 mg/d) on serum concentrations of total IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3. Design: We conducted a randomized, placebo-controlled, doubleblinded crossover study in 40 men and 31 postmenopausal women with a family history of colorectal cancer, a personal history of colorectal adenoma, or both. Results: Lycopene supplementation significantly (P ҃ 0.01) increased serum IGFBP-1 concentrations in women (median relative difference between serum IGFBP-1 concentrations after lycopene supplementation and after placebo, 21.7%). Serum IGFBP-2 concentrations were higher in both men and women after lycopene supplementation than after placebo, but to a lesser extent (mean relative difference 8.2%; 95% CI: 0.7%, 15.6% in men and 7.8%; 95% CI: Ҁ5.0%, 20.6% in women). Total IGF-I, IGF-II, and IGFBP-3 concentrations were not significantly altered by lycopene supplementation. Conclusions: This is the first study known to show that lycopene supplementation may increase circulating IGFBP-1 and IGFBP-2 concentrations. Because of high interindividual variations in IGFBP-1 and IGFBP-2 effects, these results should be confirmed in larger randomized intervention studies.Am J Clin Nutr 2007; 86:1456 -62.