Measurements of TIL density in routine clinical practice could give useful prognostic information for the triple-negative, HER2-positive, and luminal B (HER2-negative) IBC subtypes, especially for patients administered adjuvant anthracycline.

Immune rejection after transplantation is common, which leads to prompt failure of the graft. Therefore, to prolong the survival time of the graft, immunosuppressive therapy is the norm. Here, we report a robust immune protection protocol using FK506-loaded microspheres (FK506) in injectable hydrogel. Pancreatic islets were codelivered with the FK506 into the subcutaneous space of streptozocin-induced diabetic mice. The islets codelivered with 10 mg/kg FK506 maintained normal blood glucose levels during the study period (survival rate: 60%). However, transplantation of islets and FK506 at different sites hardly controlled the blood glucose level (survival rate: 20%). Immunohistochemical analysis revealed an intact morphology of the islets transplanted with FK506. In addition, minimal number of immune cells invaded inside the gel of the islet-FK506 group. The single injection of FK506 into the local microenvironment effectively inhibited immune rejection and prolonged the survival time of transplanted islets in a xenograft model.

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The results of this study suggest the IL-13 and IL-13Rα1 interaction promotes cancer cell growth and metastasis, and IL-13Rα1 expression is a potential prognostic marker in IBC.

An alternative route for pancreatic islet transplantation is the subcutaneous space; however, inadequate vascularization in the subcutaneous space limits the availability of oxygen and nutrients to the subcutaneously transplanted islets, which leads to the development of a necrotic core in the islets, thereby causing islet dysfunction. Thus, we aimed to prevent the early apoptosis of pancreatic islets after transplantation into subcutaneous space by preparing islet clusters of appropriate size. We prepared fully functional islet cell clusters (ICCs) by using the hanging-drop technique. We optimized the size of ICCs on the basis of viability and functionality after culture in an hypoxic environment. We transplanted ICCs into the subcutaneous space of diabetic mice and evaluated the viability of the islets at the transplantation site. In an hypoxic environment, ICCs exhibited improved viability and functionality compared with control islets. ICCs, upon transplantation into the hypoxic subcutaneous space of diabetic mice, showed better glycemic control compared with control islets. Live/dead imaging of the islets after retrieval from the transplanted area revealed significantly reduced apoptosis in ICCs. Transplantation of ICCs may be an attractive strategy to prevent islet cell apoptosis that results from nonimmune-mediated physiologic stress at the transplantation site.-Pathak, S., Regmi, S., Gupta, B., Pham, T. T., Yong, C. S., Kim, J. O., Yook, S., Kim, J.-R., Park, M. H., Bae, Y. K., Jeong, J.-H. Engineered islet cell clusters transplanted into subcutaneous space are superior to pancreatic islets in diabetes.

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Intratumoral CD103-positive tumour-infiltrating lymphocytes are associated with favourable prognosis in patients with triple-negative breast cancer Aims: Cluster of differentiation 103 (CD103), a marker of tissue resident memory T cells, is expressed on subsets of CD8 + T lymphocytes. We investigated the prognostic significance of CD103 + intra-epithelial tumour-infiltrating lymphocytes (iTILs) in invasive breast cancer (IBC). Methods and results: Immunohistochemistry was performed for CD103, CD8 and TGF-b isoforms (1, 2 and 3) on tissue microarrays of 1187 IBC samples. CD103 + and CD8 + iTILs were present in 904 (76.2%) and 854 (74%) cases with an overall mean AE standard deviation of 38.2 AE 100.2/mm 2 and 30.4 AE 89.7/mm 2 , respectively. The numbers of CD103 + and CD8 + iTILs were positively correlated, and CD103 + iTILs outnumbered CD8 + iTILs in HER2positive and triple-negative breast cancer (TNBC). CD103 + and CD8 + iTIL densities were significantly higher in tumours of histological grade 3, absence of lymphovascular invasion, high Ki-67 index, high stromal TIL density or TGF-b3 expression. High CD103 + iTIL density was associated with better disease-free survival (DFS, P = 0.007), but no significant association was observed for overall survival (OS). Subgroup analysis by cancer molecular subtype showed that CD103 + iTIL count was prognostic only for TNBC (OS, P = 0.035; DFS, P = 0.009). CD8 + iTIL density was significant for DFS, but not for OS, in the entire cohort and TNBC. In multivariate analysis, CD103 + iTIL density was an independent prognostic factor of OS (P = 0.02) and DFS (P = 0.007) in TNBC, while CD8 + iTIL density was not significant for survival. Conclusions: CD103 iTIL density can serve as a predictor of good prognosis in patients with TNBC.

Recent studies emphasize on developing immune tolerance by an interim administration of various immunosuppressive drugs. In this study, a robust protocol is reported for local immunomodulation using a single‐dose of FK506 microspheres and clodronate liposomes (mFK+CLO) in a xenogeneic model of islet transplantation. Surprisingly, the single‐dose treatment with mFK+CLO induce tolerance to the islet xenograft. The recipient mice display tolerogenic dendritic cells (tDCs) with decreased antigen presenting ability and T cell activation capacity. Furthermore, a reduced percentage of CD4+ and CD8+ T cells and an impaired differentiation of naïve CD4+ T cells into interferon‐γ producing Th1 and interleukin‐17 producing Th17 cells are observed. In addition, the immunosuppressive protocol leads to the generation of Foxp3+ regulatory T cells (Tregs) which are required for the long‐term graft survival. The enhanced generation of tDCs and Tregs by the single treatment of mFK+CLO cause xenograft tolerance, suggesting a possible clinical strategy which may pave the way towards improving therapeutic outcomes of clinical islet transplantation.