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.

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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.

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.

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.

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Purpose The updated American Society of Clinical Oncology/College of American Pathologists guideline for estrogen receptor (ER) testing recommends that breast cancer with ER expression in 1–10% of tumor cells should be reported as ER-low positive (ER low ), although limited data are available on the overall benefits of endocrine therapy. We investigated the clinicopathological characteristics and clinical outcomes of ER low breast cancer and to compare them with those of ER-negative (ER neg ) and ER-high (> 10% of tumor cells, ER high ) breast cancers. Methods Consecutive patients with invasive breast cancer who underwent curative surgery between November 2007 and December 2014 were included. Clinicopathological characteristics and disease-free survival (DFS) of ER low tumors were compared with those of ER neg and ER high tumors. Results Of the 2,309 cases included, 46 (2%), 643 (27.8%), and 1,620 (70.2%) were ER low , ER neg , and ER high , respectively. ER low tumors were associated with no special type of histology ( p = 0.011), advanced pT ( p = 0.017), pN ( p = 0.009) and anatomic stages ( p < 0.001), high grade ( p < 0.001), negative/low progesterone receptor (PR) status ( p < 0.001), human epidermal growth factor receptor 2 positivity ( p < 0.001), high Ki-67 ( p < 0.001), and recurrence ( p = 0.006) compared to ER high tumors. DFS was significantly dependent on ER status, and ER low tumors showed poorer DFS than ER high tumors ( p = 0.001), however, there was no significant survival difference between ER low and ER neg tumors. Furthermore, DFS in ER high patients was affected by hormone therapy ( p < 0.001), while it was not affected in ER low patients. Conclusion Patients with ER low breast cancer have clinicopathological characteristics that differ from those with ER high tumors. Although this study was limited by the small sample size of the ER low group, no benefit from hormone therapy was observed in the ER low group compared with the ER high group.