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Anti-Müllerian hormone (AMH) [also called Müllerian inhibiting substance (MIS)] is a member of the transforming growth factor-beta family. AMH and its type II receptor (AMHR-II) are involved in the regression of the Müllerian ducts in the male embryo, and in gonadal functions in the adult. AMH is also known to be a marker of granulosa and Sertoli cell tumours. We selected a high-affinity monoclonal antibody, mAb 12G4, specific for human AMHR-II (hAMHR-II), by FACS analysis, Western blotting and immunohistochemical staining of a hAMHR-II-transfected CHO (Chinese hamster ovary) cell line, normal adult testicular tissue and granulosa cell tumours. Using peptide array screening, we identified the binding sequences of mAb 12G4 and AMH on the receptor. Identification of Asp53 and Ala55 as critical residues in the DRAQVEM minimal epitopic sequence of mAb 12G4 definitively accounted for the lack of cross-reactivity with the murine receptor, in which there is a glycine residue in place of an aspartic acid residue. In a structural model, the AMH-binding interface was mapped to the concave side of hAMHR-II, whereas the mAb 12G4-binding site was located on the convex side. mAb 12G4, the first mAb to be raised against hAMHR-II, therefore has unique properties that could make it a valuable tool for the immunotargeting of tumours expressing this receptor.

Eggshell has been recently introduced as a bone substitute candidate in reconstructive surgery. The aim of this experimental study study was to determine its degradation rate in both a skeletal and extraskeletal site. In experiment 1, eggshell particles with four different sizes (50, 75, 150, and 300 microns in diameter) were implanted in subcutaneous pouches of 30 rats. In experiment 2, a fragment of ostrich eggshell was implanted on the nasal dorsum of 10 rats. Animals were sacrificed at 1 (N = 10), 2 (N = 10), and 4 months (N = 10) during the first stage of the study, and at 1 year during the second stage of the study. The results were assessed by X-ray examination and routine histological techniques. In experiment 1, all animals healed uneventfully. At 1 month, only 50-micron particles had undergone resorption. At 2 months, both 50- and 75-micron particles had undergone resorption. At 4 months, the 150- and 300-micron particles were resorbed incompletely. Histologically, the eggshell elicited a mild inflammatory reaction at 1 month that decreased progressively at further stages. In experiment 2, all animals except one healed uneventfully. Radiologically, the eggshell implant displayed a noticeable stability. Histologically, seven of nine implants were encapsulated, but two of them were surrounded by a bony rim. In conclusion, eggshell is a resorbable implant, but the degradation kinetic is size dependent. Large ostrich grafts are also suitable as onlay graft, but a complementary osteosynthesis is recommended to enhance osteointegration.

T cells contribute to the immune response against many cancers, notably through their powerful effector functions that lead to the elimination of tumor cells and the recruitment of other immune cells. However, their presence in the tumor microenvironment has been associated with poor prognosis in breast, colon, and pancreatic cancer, suggesting that T cells may also display pro-tumor activities. Here, we identified in blood from healthy donors a subpopulation of V 1T cells that represents around 20% of the whole V 1 population, expresses CD73, and displays immunosuppressive phenotype and functions (i.e., production of immunosuppressive molecules, such as IL-10, adenosine, and the chemotactic factor IL-8, and inhibition of T cell proliferation). We then found that in human breast tumors, T cells were present particularly in late stage breast cancer samples, and that ∼20% of tumor-infiltrating T cells expressed CD73. Taken together, these results suggest that regulatory T cells are present in the breast cancer microenvironment and may display immunosuppressive functions through the production of immunosuppressive molecules, such as IL-10, IL-8, and adenosine, thus promoting tumor growth. K E Y W O R D S immunosuppression, non-conventional T cells, tumor microenvironment 1 INTRODUCTION T cells are nonconventional lymphocytes defined by the expression of a specific receptor composed of the V and V chains. In humans, there are 2 main subtypes of T cells, according to the expressed V chain: (i) V 2 T cells, mainly represented by the innate V 9V 2 T cell subset that is predominant in blood and recognizes phosphorylated non-peptide Ags called phosphoantigens; and (ii) non-V 2 T cells (mainly represented by the V 1 subset) that are predominant in tissues

Advanced Epithelial Ovarian Cancer (EOC) patients frequently relapse by 24 months and develop resistant disease. Research on EOC therapies relies on cancer cell lines established decades ago making Patient Derived Xenografts (PDX) attractive models, because they are faithful representations of the original tumor. We established 35 ovarian cancer PDXs resulting from the original graft of 77 EOC samples onto immuno-compromised mice. PDXs covered the diversity of EOC histotypes and graft take was correlated with early patient death. Fourteen PDXs were characterized at the genetic and histological levels. PDXs reproduced phenotypic features of the ovarian tumors of origin and conserved the principal characteristics of the original copy number change (CNC) profiles over several passages. However, CNC fluctuations in specific subregions comparing the original tumor and the PDXs indicated the oligoclonal nature of the original tumors. Detailed analysis by CGH, FISH and exome sequencing of one case, for which several tumor nodules were sampled and grafted, revealed that PDXs globally maintained an oligoclonal structure. No overgrowth of a particular subclone present in the original tumor was observed in the PDXs. This suggested that xenotransplantation of ovarian tumors and growth as PDX preserved at least in part the clonal diversity of the original tumor. We believe our data reinforce the potential of PDX as exquisite tools in pre-clinical assays.

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