A fully defined 3D matrix for ex vivo expansion of human colonic organoids from biopsy tissue.

Intestinal organoids have widespread research and biomedical applications, such as disease modeling, drug testing and regenerative medicine. However, the transition towards clinical use has in part been hampered by the dependency on animal tumor-derived basement membrane extracts (BMEs), which are poorly defined and ill-suited for regulatory approval due to their origin and batch-to-batch variability. In order to overcome these limitations, and to enable clinical translation, we tested the use of a fully defined hydrogel matrix, QGel CN99, to establish and expand intestinal organoids directly from human colonic biopsies.

Attenuation of the pro-inflammatory signature of lung cancer-derived mesenchymal stromal cells by statins.

Solid tumor growth triggers a dynamic host response, which recapitulates wound healing and defines the tumor microenvironment (TME). In addition to the action of the tumor cells themselves, the TME is maintained by a myriad of immune and stromal cell-derived soluble mediators and extracellular matrix components whose combined action supports tumor progression. However, therapeutic targeting of the TME has proven challenging because of incomplete understanding of the tumor-host crosstalk at the molecular level.

Reciprocal modulation of mesenchymal stem cells and tumor cells promotes lung cancer metastasis.

Metastasis is a multi-step process in which direct crosstalk between cancer cells and their microenvironment plays a key role. Here, we assessed the effect of paired tumor-associated and normal lung tissue mesenchymal stem cells (MSCs) on the growth and dissemination of primary human lung carcinoma cells isolated from the same patients. We show that the tumor microenvironment modulates MSC gene expression and identify a four-gene MSC signature that is functionally implicated in promoting metastasis.

Tumor-Derived Mesenchymal Stem Cells Use Distinct Mechanisms to Block the Activity of Natural Killer Cell Subsets.

Mesenchymal stem cells (MSCs) display pleiotropic functions, which include secretion of soluble factors with immunosuppressive activity implicated in cancer progression. We compared the immunomodulatory effects on natural killer (NK) cells of paired intratumor (T)- and adjacent non-tumor tissue (N)-derived MSCs from patients with squamous cell lung carcinoma (SCC). We observed that T-MSCs were more strongly immunosuppressive than N-MSCs and affected both NK function and phenotype, as defined by CD56 expression.

NKp30 isoforms and NKp46 transcripts in metastatic melanoma patients: Unique NKp30 pattern in rare melanoma patients with favorable evolution.

Given the NK cell-based immunosurveillance of melanoma, we investigated the prognostic value of NKp46 transcript and NKp30 isoform (NKp30A, NKp30B and NKp30C) profiling in blood of 187 melanoma patients including 13 long survivors (LS), metastatic patients that have controlled the disease. Compared to healthy volunteers (HV), patients had reduced amounts of transcripts of the three NKp30 isoforms (NKp30 A, B and C) but similar ratios between NKp30 isoforms (ΔAB, ΔAC, ΔBC). Stratification of patients according to disease stage showed higher NKp30C and lower NKp46 transcripts in stage IV patients.

The fusion protein SS18-SSX1 employs core Wnt pathway transcription factors to induce a partial Wnt signature in synovial sarcoma.

Expression of the SS18/SYT-SSX fusion protein is believed to underlie the pathogenesis of synovial sarcoma (SS). Recent evidence suggests that deregulation of the Wnt pathway may play an important role in SS but the mechanisms whereby SS18-SSX might affect Wnt signaling remain to be elucidated. Here, we show that SS18/SSX tightly regulates the elevated expression of the key Wnt target AXIN2 in primary SS.

Characterization of the Microenvironment in Positive and Negative Sentinel Lymph Nodes from Melanoma Patients.

Melanomas are aggressive skin tumors characterized by high metastatic potential. Our previous results indicate that Natural Killer (NK) cells may control growth of melanoma. The main defect of blood NK cells was a decreased expression of activating NCR1/NKp46 receptor and a positive correlation of NKp46 expression with disease outcome in stage IV melanoma patients was found.

Mature cytotoxic CD56(bright)/CD16(+) natural killer cells can infiltrate lymph nodes adjacent to metastatic melanoma.

Melanomas are characterized by high metastatic potential, with regional lymph node representing the most frequent site of early dissemination in this disease. These regional lymph nodes also represent the primary site for differentiation of natural killer (NK) cells. Although blood-derived NK cells can efficiently lyse melanoma cells isolated from metastatic lymph node (M-LN), there has been no study of the properties of the most disease-relevant NK cells isolated from M-LN in patients with melanoma.

Phenotypic and functional characteristics of blood natural killer cells from melanoma patients at different clinical stages.

Melanomas are aggressive skin tumors characterized by high metastatic potential. Immunotherapy is a valuable alternative for metastatic melanoma patients resistant to chemotherapy. Natural Killer (NK) cells are efficient anti-tumor cytotoxic effectors.

High number of CD56(bright) NK-cells and persistently low CD4+ T-cells in a hemophiliac HIV/HCV co-infected patient without opportunistic infections.

Background: Both the human immunodeficiency virus (HIV) and hepatitis C virus (HCV), either alone or as coinfections, persist in their hosts by destroying and/or escaping immune defenses, with high morbidity as consequence. In some cases, however, a balance between infection and immunity is reached, leading to prolonged asymptomatic periods. We report a case of such an indolent co-infection, which could be explained by the development of a peculiar subset of Natural Killer (NK) cells.

NK cells sense tumors, course of disease and treatments: Consequences for NK-based therapies.

The recent findings on NK activation indicate that these cells are important antitumor effectors. NK cells participate in the graft-vs.-leukemia effect to control the relapse in leukemic patients transplanted with allogeneic hematopoietic stem cells.

Serum soluble HLA-E in melanoma: a new potential immune-related marker in cancer.

Background: Tumor-derived soluble factors, including soluble HLA molecules, can contribute to cancer immune escape and therefore impact on clinical course of malignant diseases. We previously reported that melanoma cells produce, in vitro, soluble forms of the non-classical MHC class I molecule HLA-E (sHLA-E). In order to investigate sHLA-E production by various tumors and to address its potential value as a tumor-associated marker, we developed a specific ELISA for the quantification of sHLA-E in biological fluids.

Unique functional status of natural killer cells in metastatic stage IV melanoma patients and its modulation by chemotherapy.

Purpose: Immunotherapy is an alternative for metastatic melanoma patients resistant to chemotherapy. Natural killer (NK) cells are powerful antileukemia effectors and their role in solid tumors is suspected. NK cell activation is regulated by a balance between activating receptors, which detect stress molecules on tumor cells, and HLA-I specific inhibitory receptors.