Human Wnt/ß-Catenin Regulates Alloimmune Signaling during Allogeneic Transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most widely applied forms of adoptive immunotherapy for the treatment of hematological malignancies. Detrimental graft-versus-host disease (GVHD), but also beneficial graft-versus-leukemia (GVL) effects occurring after allo-HSCT are largely mediated by alloantigen-reactive donor T cells in the graft. Separating GVHD from GVL effects is a formidable challenge, and a greater understanding of donor T cell biology is required to accomplish the uncoupling of GVHD from GVL. Here, we evaluated the role of ß-catenin in this process. Using a unique mouse model of transgenic overexpression of human ß-catenin (Cat-Tg) in an allo-HSCT model, we show here that T cells from Cat-Tg mice did not cause GVHD, and surprisingly, Cat-Tg T cells maintained the GVL effect. Donor T cells from Cat-Tg mice exhibited significantly lower inflammatory cytokine production and reduced donor T cell proliferation, while upregulating cytotoxic mediators that resulted in enhanced cytotoxicity. RNA sequencing revealed changes in the expression of 1169 genes for CD4, and 1006 genes for CD8+ T cells involved in essential aspects of immune response and GVHD pathophysiology. Altogether, our data suggest that ß-catenin is a druggable target for developing therapeutic strategies to reduce GVHD while preserving the beneficial GVL effects following allo-HSCT treatment.

A rare occurrence of basal cell adenoma of palate: A case report with comprehensive immunohistochemical analysis.

Basal cell adenoma (BCA) of the salivary glands is an uncommon type of monomorphic adenoma which constitutes 1% of all salivary gland tumors. It most commonly involves parotid gland, while it rarely occurs in minor salivary glands. Upper lip, buccal mucosa, and lower lip are the common intraoral sites; whereas, palate being the rarest one. Due to prognostic implications, differential diagnosis with basal cell adenocarcinoma, basaloid squamous cell carcinoma, and adenoid cystic carcinoma (AdCC) is mandatory. Considering the rarity of this lesion and histologic paradox regarding its diagnosis, we report a case of BCA of palate with emphasis on need of comprehensive immunohistochemical (IHC) analysis.