Celiac disease, also known as “celiac sprue”, is a chronic inflammatory disorder of the small intestine, produced by the ingestion of dietary gluten products in susceptible people. It is a multifactorial disease, including genetic and environmental factors. Environmental trigger is represented by gluten while the genetic predisposition has been identified in the major histocompatibility complex region. Celiac disease is not a rare disorder like previously thought, with a global prevalence around 1%. The reason of its under-recognition is mainly referable to the fact that about half of affected people do not have the classic gastrointestinal symptoms, but they present nonspecific manifestations of nutritional deficiency or have no symptoms at all. Here we review the most recent data concerning epidemiology, pathogenesis, clinical presentation, available diagnostic tests and therapeutic management of celiac disease.
Breast carcinoma is a major health issue for millions of women. Current therapies have serious side effects, and are only partially effective in patients with metastatic tumors. Thus, the need for novel and less toxic therapies is urgent. Moreover, hormonal and antibody therapies effective in other subtypes are not effective in Triple Negative Breast Cancer (TNBC). Immunotherapeutic strategies directed against specific tumor-associated antigens (TAAs) and mediated by specific cytotoxic T lymphocytes (CTL) have been largely underexplored in this disease. Cancer-testis antigens (CTA) are a group of TAAs displaying the ideal characteristics of promising vaccine targets, i.e. strong immunogenicity and cancer specificity. The CTA, Sperm Protein 17 (SP17), has been found to be aberrantly expressed in different neoplasms, including ovarian and esophageal cancers, nervous system tumors and multiple myeloma, and has been suggested as a candidate target for immunotherapy.Here, we evaluated SP17 expression levels in breast cancer cell lines, invasive ductal breast carcinoma, including patients with TNBC, and adjacent non-neoplastic breast tissue, and determined whether SP17 was capable of generating SP17-specific cytotoxic T lymphocytes in vitro.We showed that SP17 is expressed in breast cancer cell lines and primary breast tumors and importantly in TNBC subtype, but not in adjacent non-tumoral breast tissue or unaffected tissues, except in male germinal cells. Furthermore, we detected specific anti-SP17 antibodies in patients’ sera and we generated SP17-specific, HLA class I-restricted, cytotoxic T lymphocytes capable of efficiently killing breast cancer cells.
Background: Tumor sorrounding stroma and cancer associated fibroblast (CAFs) in particular play a major role in ductal adenocarcinoma of the pancreas (PDAC). The aim of our study was to r investigate the interaction between CAFs and PDAC cells in vitro using patient derived CAF cultures. Methods: CAFs were isolated from tumor tissue, transferred to in vitro setting and phenotypically characterized. Migration capacity and chemo-sensitivity was evaluated in a modified two-well system with established PDAC cell lines. Non-malignant fibroblast from foreskin served as controls. Paracrine interaction via chemokines was measured using elisa. Results: CAFs resemble activated pancreatic stellate cells. A strong negative effect on the therapeutic response of PDAC cells to Gemcitabine, Notch inhibition (DAPT) and nab-paclitaxel could be observed in direct co-cultures. Indirect co-culturing showed no significant effect on the chemo-sensitivity of PDAC cells but nevertheless resulted in a significant increase of IL-6 levels. PDAC cells showed a higher migration capacity when cocultured with CAFs. CAFs themselves showed a significantly higher migration capacity compared to non-malignant fibroblasts. This was further boosted in presence of PDAC cells. Conclusion: We elucidated a strong interaction between PDAC cells and CAFs, which may have a high impact on therapeutic efficiency. Paracrine inflammation response could play a pivotal role in this modification process. Further evaluation is needed to clarify this observations.
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