Epithelial tumor suppressor ELF3 is a lineage-specific amplified oncogene in lung adenocarcinoma.

Gene function in cancer is often cell type-specific. The epithelial cell-specific transcription factor ELF3 is a documented tumor suppressor in many epithelial tumors yet displays oncogenic properties in others. Here, we show that ELF3 is an oncogene in the adenocarcinoma subtype of lung cancer (LUAD), providing genetic, functional, and clinical evidence of subtype specificity.

Pan-specific and partially selective dye-labeled peptidic inhibitors of the polycomb paralog proteins.

Epigenetic regulation of gene expression is in part controlled by post-translational modifications on histone proteins. Histone methylation is a key epigenetic mark that controls gene transcription and repression. There are five human polycomb paralog proteins (Cbx2/4/6/7/8) that use their chromodomains to recognize trimethylated lysine 27 on histone 3 (H3K27me3).

Identification and Analyses of Extra-Cranial and Cranial Rhabdoid Tumor Molecular Subgroups Reveal Tumors with Cytotoxic T Cell Infiltration.

Extra-cranial malignant rhabdoid tumors (MRTs) and cranial atypical teratoid RTs (ATRTs) are heterogeneous pediatric cancers driven primarily by SMARCB1 loss. To understand the genome-wide molecular relationships between MRTs and ATRTs, we analyze multi-omics data from 140 MRTs and 161 ATRTs. We detect similarities between the MYC subgroup of ATRTs (ATRT-MYC) and extra-cranial MRTs, including global DNA hypomethylation and overexpression of HOX genes and genes involved in mesenchymal development, distinguishing them from other ATRT subgroups that express neural-like features.

Canadian Tissue Repository Network Biobank Certification Program: Update and Review of the Program from 2011 to 2018.

The Canadian Tissue Repository Network (CTRNet) Biobank Certification Program was first launched in 2011 to foster translational research through improved access to high quality biospecimens. This was accomplished by creating and providing biobank education and through the establishment and deployment of common standards to harmonize biospecimen quality and approaches to governance. The CTRNet program comprises registration and certification steps as two linked phases.

Biospecimen Complexity and the Evolution of Biobanks.

Biospecimens are critical in driving health research. There is increased demand for scale and quality of biospecimens that in turn drives biobanking operational costs, influences utilization, and threatens the sustainability of individual biobanks. Biospecimen research has begun to inform the details of new biobanking standards and the steps of the biobanking process that are most important to focus on to achieve higher quality.

Autophagy metabolically suppresses CD8 T cell antitumor immunity.

Macroautophagy/autophagy is a critical regulator of adaptive T cell immunity and homeostasis. However, the role of T cell autophagy in regulating antitumor immune responses is less clear. In a recent study, we showed that deletion of the essential autophagy genes , or in host tissues dramatically impairs growth of autophagy-competent syngeneic tumors.

Raman spectroscopy detects metabolic signatures of radiation response and hypoxic fluctuations in non-small cell lung cancer.

Background: Radiation therapy is a standard form of treating non-small cell lung cancer, however, local recurrence is a major issue with this type of treatment. A better understanding of the metabolic response to radiation therapy may provide insight into improved approaches for local tumour control. Cyclic hypoxia is a well-established determinant that influences radiation response, though its impact on other metabolic pathways that control radiosensitivity remains unclear.

Going to extremes: determinants of extraordinary response and survival in patients with cancer.

Research into factors affecting treatment response or survival in patients with cancer frequently involves cohorts that span the most common range of clinical outcomes, as such patients are most readily available for study. However, attention has turned to highly unusual patients who have exceptionally favourable or atypically poor responses to treatment and/or overall survival, with the expectation that patients at the extremes may provide insights that could ultimately improve the outcome of individuals with more typical disease trajectories. While clinicians can often recount surprising patients whose clinical journey was very unusual, given known clinical characteristics and prognostic indicators, there is a lack of consensus among researchers on how best to define exceptional patients, and little has been proposed for the optimal design of studies to identify factors that dictate unusual outcome.

Biospecimen Data Reporting in the Research Literature.

A substantial fraction of biomedical research depends on the reliability of human biospecimens but variations in sample manipulation during collection, processing, and storage can differentially alter molecular integrity and influence interpretation of the resulting derived data. Details of biobanking processes are rarely adequately described in research publications, preventing reviewers, readers, and scientists seeking to replicate the findings, from appreciating and adequately considering preanalytical variations contributing to results. To address these shortcomings, a set of reporting guidelines, the Biospecimen Reporting for Improved Study Quality (BRISQ) criteria, were developed in 2011.

Cancer stemness, intratumoral heterogeneity, and immune response across cancers.

Regulatory programs that control the function of stem cells are active in cancer and confer properties that promote progression and therapy resistance. However, the impact of a stem cell-like tumor phenotype ("stemness") on the immunological properties of cancer has not been systematically explored. Using gene-expression-based metrics, we evaluated the association of stemness with immune cell infiltration and genomic, transcriptomic, and clinical parameters across 21 solid cancers.

Autophagy Regulation of Metabolism Is Required for CD8 T Cell Anti-tumor Immunity.

Autophagy is a cell survival process essential for the regulation of immune responses to infections. However, the role of T cell autophagy in anti-tumor immunity is less clear. Here, we demonstrate a cell-autonomous role for autophagy in the regulation of CD8 T-cell-mediated control of tumors.

The effect of diet and exercise on tobacco carcinogen-induced lung cancer.

In previous studies, we found that low-carbohydrate (CHO) diets reduced the incidence of tumors in mice genetically predisposed to cancer. However, because >90% of human cancers arise via carcinogen-induced somatic mutations, we investigated, herein, the role that different types and levels of CHO, protein and lipid play in lung cancer induced by the tobacco-specific carcinogen, nicotine-derived nitrosamine ketone (NNK) in A/J mice. We found lowering CHO levels significantly reduced lung nodules and blood glucose levels.

A Transcriptionally Distinct CXCL13CD103CD8 T-cell Population Is Associated with B-cell Recruitment and Neoantigen Load in Human Cancer.

The chemokine CXCL13 mediates recruitment of B cells to tumors and is essential for the formation of tertiary lymphoid structures (TLSs). TLSs are thought to support antitumor immunity and are associated with improved prognosis. However, it remains unknown whether TLSs are formed in response to the general inflammatory character of the tumor microenvironment, or rather, are induced by (neo)antigen-specific adaptive immunity.

Haralick texture feature analysis for quantifying radiation response heterogeneity in murine models observed using Raman spectroscopic mapping.

Tumour heterogeneity plays a large role in the response of tumour tissues to radiation therapy. Inherent biological, physical, and even dose deposition heterogeneity all play a role in the resultant observed response. We here implement the use of Haralick textural analysis to quantify the observed glycogen production response, as observed via Raman spectroscopic mapping, of tumours irradiated within a murine model.

Interaction of Treponema pallidum, the syphilis spirochete, with human platelets.

Extracellular bacteria that spread via the vasculature employ invasive mechanisms that mirror those of metastatic tumor cells, including intravasation into the bloodstream and survival during hematogenous dissemination, arrestation despite blood flow, and extravasation into distant tissue sites. Several invasive bacteria have been shown to exploit normal platelet function during infection. Due to their inherent ability to interact with and influence other cell types, platelets play a critical role in alteration of endothelial barrier permeability, and their role in cancer metastasis has been well established.

Hyperspectral cell sociology reveals spatial tumor-immune cell interactions associated with lung cancer recurrence.

Background: The tumor microenvironment (TME) is a complex mixture of tumor epithelium, stroma and immune cells, and the immune component of the TME is highly prognostic for tumor progression and patient outcome. In lung cancer, anti-PD-1 therapy significantly improves patient survival through activation of T cell cytotoxicity against tumor cells. Direct contact between CD8+ T cells and target cells is necessary for CD8+ T cell activity, indicating that spatial organization of immune cells within the TME reflects a critical process in anti-tumor immunity.

Research Perspective on Utilizing and Valuing Tumor Biobanks.

Tumor biobanks have become critical components of the cancer research infrastructure. Consideration of how to place appropriate values on tumor biobanks is important for all stakeholders. At the level of individual biobanks, value is important in determining how to contribute to, utilize, and fund biobanks.

Somatic mutation-associated T follicular helper cell elevation in lung adenocarcinoma.

T follicular helper cells (Tfh) play crucial roles in the development of humoral immunity. In the B cell-rich germinal center of lymphoid organs, they select for high-affinity B cells and aid in their maturation. While Tfh have known roles in B cell malignancies and have prognostic value in some epithelial cancers, their role in lung tumour initiation and development is unknown.

Adoptive cell therapy with tumor-infiltrating lymphocytes in patients with metastatic ovarian cancer: a pilot study.

:Ovarian cancer (OC) is often diagnosed at an advanced stage with two thirds of patients experiencing recurrent disease with a poor prognosis. Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has shown curative potential in malignant melanoma, but has only been investigated scarcely in other cancers. In this pilot study, we tested TIL based ACT in patients with metastatic OC.

Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers.

Infiltration of human cancers by T cells is generally interpreted as a sign of immune recognition, and there is a growing effort to reactivate dysfunctional T cells at such tumor sites. However, these efforts only have value if the intratumoral T cell receptor (TCR) repertoire of such cells is intrinsically tumor reactive, and this has not been established in an unbiased manner for most human cancers. To address this issue, we analyzed the intrinsic tumor reactivity of the intratumoral TCR repertoire of CD8 T cells in ovarian and colorectal cancer-two tumor types for which T cell infiltrates form a positive prognostic marker.

Genetics and Genomics of an Unusual Selfish Sex Ratio Distortion in an Insect.

Diverse selfish genetic elements have evolved the ability to manipulate reproduction to increase their transmission, and this can result in highly distorted sex ratios [1]. Indeed, one of the major explanations for why sex determination systems are so dynamic is because they are shaped by ongoing coevolutionary arms races between sex-ratio-distorting elements and the rest of the genome [2]. Here, we use genetic crosses and genome analysis to describe an unusual sex ratio distortion with striking consequences on genome organization in a booklouse species, Liposcelis sp.