Tumour-infiltrating lymphocytes (TILs) signify immune response to tumour in a variety of cancers including breast cancer. However, earlier studies examining the clinical significance of TILs in breast cancers have generated mixed results. There are only a few that address the relationship between TILs and clinical outcomes in triple-negative breast cancers (TNBC). The aim of this study is to evaluate the clinical significance of TILs that express CD4 + and CD8 + , in TNBC. Immunohistochemical staining of CD4 and CD8 was performed on tissue microarrays of 164 cases of TNBC. TILs were counted separately as intratumoral when within the cancer cell nests (iTILs) and as stromal when within cancer stroma (sTILs). High CD8 + iTILs and sTILs, and CD4 + iTILs correlated with histologic grade. On Kaplan-Meier analysis, a significantly better survival rate was observed in high CD8 + iTIL (disease-free survival, DFS: P = 0.004, overall survival, OS: P = 0.02) and both high CD4 + iTILs (DFS: P = 0.025, OS: P = 0.023) and sTILs (DFS: P = 0.01, OS: P = 0.002). In multivariate analysis, CD8 + iTILs (DFS: P = 0.0095), CD4 + sTILs (DFS: P = 0.0084; OS: P = 0.0118), and CD4 (high) CD8 (high) CD8 iTILs (DFS: P = 0.0121; OS: P = 0.0329) and sTILs (DFS: P = 0.0295) showed significantly better survival outcomes. These results suggest that high levels of both CD8 + iTILs and CD4 + sTILs as well as CD4 (high) CD8 (high) iTILs and sTILs are independent prognostic factors in TNBC.

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

Triple negative breast cancer (TNBC) is a heterogenous disease often characterised by aggressive biology and poor prognosis. Efforts to precisely treat TNBC have been compounded by the lack of specific therapeutic molecular targets. Recent transcriptomic studies have revealed, among others, an immunomodulatory subtype of TNBC, whereby activated immune response genes are associated with good prognosis. Since then, a great deal of effort has been made to understand the immune microenvironment of some TNBC subtype, which comprises several immune cell populations including lymphocytes and macrophages. There is increasing evidence that the basal subtype may be significantly regulated by tumour-infiltrating T-cells and that high levels of tumour-infiltrating CD8+ T-cells may be a reflection of improved prognosis with chemotherapy sensitivity in TNBC. On the other hand, tumour-associated macrophages have been associated with a relatively poor outcome in TNBC. Comparison of the immune signatures in TNBC with non-TNBC may furthermore help us to understand these immune mechanisms potentially leading to new therapeutic approaches. Within this short review, we discuss the current scientific evidence regarding (a) the role of tumour-infiltrating lymphocytes in the clinical outcome in TNBC and (b) the newly discovered immunomodulatory genotype that may provide for a therapeutic target in TNBC.

Tubulocystic carcinoma of the kidney (TCK) is a recently established entity in renal neoplastic pathology. This review aims to give an overview of the clinical and pathobiological aspects of TCK. Grossly, the TCKs are well-demarcated multicystic lesions giving a "wrapped bubble" or "spongy" appearance. Microscopically, the tumors are composed of multiple, variably sized cysts separated by thin fibrous septa lacking ovarian stroma or desmoplastic reaction. The cysts are lined by tumor cells with eosinophilic cytoplasm and nuclear atypia of variable, but not infrequently of high grade corresponding to Fuhrman grade 3. A frequent association with papillary tumors has been reported. Recent molecular genetic studies of TCK have revealed distinct features separating this subset of renal cell carcinomas (RCCs) from other types of renal tumors including collecting duct carcinoma of Bellini and renal medullary carcinoma as well as pointing towards a close kinship with papillary RCC. Tubulocystic carcinoma of the kidney generally pursues an indolent clinical course. However, several cases with aggressive clinical behavior have been reported. We strongly feel that there is enough clinicopathological evidence to corroborate TCK as a separate entity and that it should be incorporated into the next WHO classification of renal tumors as a separate neoplastic category.

Background: Both BAG6 and Ubl4a are mediators of tail-anchored (TA) protein biogenesis and protein quality control.Results: The crystal structure of the BAG6-Ubl4a heterodimerization domain reveals a unique binding interface.Conclusion: The BAG-similar domain of BAG6 is completely distinct from other canonical BAG domains.Significance: Ubl4a forms a complex with BAG6, whereas its yeast homologue Get5 forms a homodimer.