HostSeq: a Canadian whole genome sequencing and clinical data resource.

HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

A novel schistosome species hosted by Planorbella (Helisoma) trivolvis is the most widespread swimmer's itch-causing parasite in Michigan inland lakes.

Cercarial dermatitis ('swimmer's itch'; SI), characterized by small itchy bumps caused by schistosome parasites of birds and mammals, is a common problem in Michigan. Research on avian schistosomes began nearly 100 years ago in Michigan inland lakes, yet scientists are still uncovering basic biological information including the identification of local snail and parasite species that cause SI. Previous research primarily focused on lakes in the northern half of Michigan's lower peninsula, although SI occurs throughout the state. We surveyed snails and snail-borne trematodes in lakes across Michigan's lower peninsula and used quantitative polymerase chain reaction analysis of filtered water samples to identify parasites to the species level, including a recently discovered parasite species that uses the snail Planorbella (Helisoma) trivolvis as its intermediate host. Most SI mitigation efforts have focused on a parasite species hosted by the snail Lymnaea catescopium ( = Stagnicola emarginata); however, lymnaeid snails and their associated schistosome species were largely restricted to northern lakes. In contrast, P. trivolvis and its associated parasite species were common in both northern and southern Michigan lakes. A third schistosome species associated with physid snails was also present at low levels in both northern and southern lakes. These results indicate that the recently discovered parasite species and its planorbid snail intermediate host may be more important drivers of Michigan SI than previously thought, possibly due to increased definitive host abundance in recent decades. These results have potentially important implications for SI mitigation and control efforts.

Outcomes of Kidney Transplant During the SARS-CoV-2 Pandemic at 1 Center in Poland.

The SARS-CoV-2 pandemic has significantly affected the number of transplanted organs worldwide. The rules and restrictions related to transplantation activities in Poland are included in the updated guidelines of the Polish Organizational and Coordination Centre for Transplantation. Our clinic faces the same problems as the rest of the hospitals in the country. Not only are the number of recipients falling, but there are also numerous restrictions concerning, among other things, qualification of donors and recipients and even preparation of centers for long-term care in the event of infection of organ recipients with the SARS-CoV-2 virus. Statistics showed, after an initial fall in the number of kidneys transplanted, a temporary normalization during the summer months, only to record a fall again with an increase in new cases of COVID-19. A total of 29 kidneys were transplanted at our center between March and December 2020. Kidney transplantation is not only linked to the operation itself, but also to the follow-up care of the recipients. Reduced immunity among recipients due to immunosuppressive treatment as well as comorbidities among recipients contribute to this group being at increased risk of symptomatic SARS-CoV-2 infection. The number of cases of SARS-CoV-2 infection among kidney transplant recipients at our center was 7, of which we recorded 2 deaths due to COVID-19 in the period after kidney transplant. Postoperative complications probably related to previous SARS-CoV-2 infection occurred in 1 patient.

The Arterial Anastomosis Between Deep Inferior Epigastric Artery and Small Polar Renal Artery in Kidney Transplantation: A Case Report.

The presence of multiple renal arteries is the most common form of vascular anomalies found in donor kidneys. In rare cases, small renal polar arteries may be found. They can be anastomosed with deep inferior epigastric arteries, resulting in vascular augmentation of transplanted kidneys and contributing to better graft function. Renal perfusion may be increased via 2 types of vascular reconstruction known as "turbocharging" and "supercharging". Turbocharging uses vascular sources within the same organ area, whereas supercharging uses distant vascular sources. Using additional vessels can either complicate the surgery or, contradictorily, ease the way of procedure. This case study presents a kidney transplant during which arterial anastomosis between deep inferior epigastric artery and small polar renal artery was performed.

Transplantation of a Kidney With Duplicated Ureter Harvested From a Donor With Vascular Anomaly in the Form of Double Inferior Vena Cava: A Case Report.

During the organ procurement procedure, a surgeon encounters anatomic anomalies not very often but also not uncommonly. These changes may put the success of the transplant into question. Despite the thorough diagnosis of the potential donor, these anomalies are often diagnosed during organ donation. In our paper we present a case of kidney transplantation with duplicated ureter. The organ was collected from a donor with duplicated inferior vena cava. After transplantation, the kidney functioned immediately. Taking into consideration the well-being of the recipient, organs with anatomic abnormalities should be carefully considered for transplantation. This is especially important when there is a constant shortage of organs for transplantation.

Correlation Between Percentage of Immuncompetent CD4+ and CD4+CD25+ Cells and Compatibility in the HLA System and Selected Parameters Assessing Transplanted Kidney Function.

BACKGROUND: Long-term kidney allograft survival is affected by many coexisting immunologic factors. Currently, only two basic immunologic parameters-HLA compatibility and panel reactive antibodies-are routinely used in kidney transplantation management. At the same time, there is a great need for immunologic biomarkers that will help inrease understanding of kidney transplant immunology and improve clinical care of kidney recipients. T regulatory cells (Tregs) represent one of the major targets of this approach. The aim of this study was to investigate possible simple associations between Tregs count in recipients' blood and other routinely assessed or easily accessible laboratory parameters. METHODS: Laboratory outcomes from medical files of transplant outpatient clinic in combination with flow cytometry analyses of particular immunocompetent cells populations were used. Flow cytometry was used to calculate Tregs recognized as TCD4+CD25high. The Spearman rank correlation test was used to verify particular associations. RESULTS: A negative correlation was found beween HLA compatibility and Tregs count as well as between platelets count and Tregs count. CONCLUSIONS: Whereas the negative correlation between Tregs and platelets counts may possibly mirror some recent findings in basic research, a negative correlation between HLA compatibility and Tregs points the direction of further research to factors triggering post-transplant immune tolerance.

The Importance of New Generation Sequencing (NGS) HLA Typing in Renal Transplantation-Preliminary Report.

INTRODUCTION: Thanks to new generation sequencing (NGS) and expansion of HLA typing with additional loci, it will be possible to increase the effectiveness of graft survival and to avoid complications related to the immune system. New pharmacogenetic factors are still being researched to develop better immunosuppressive treatment. MATERIAL AND METHODS: The incidence of polymorphic HLA loci variants was established, based on a high-resolution NGS method in kidney graft recipients. Furthermore, haplotypic analysis between examined loci was conducted to type additional loci that may influence the transplantation result. A total of 120 kidney recipients were enrolled in the study. A commercial DNA extraction kit in Tubes (QIAamp DNA Blood Mini Kit Qiagen, Germany) was used to isolate DNA from the blood. Sequencing library preparation was done with TruSight HLA set. The Conexio computer program was used to analyse the results of HLA typing. RESULTS: The patients with alleles A*02:01:01, B*44:02:01, C*03:03:01, C*01:02:01, C*05:01:01, C*07:02:01, DQB1*03:03:02, DQB1*06:04:01, or with haplotypic variation A*25:01:01-B*18:01:01- C*15:01:01 were taking the highest doses of cyclosporine (CsA), in contrast to patients with allele B*18:01:01, DQB1*06:02:01, DQB1*02:02:01, or haplotypic variation A*02:01:01- B*44:02:01-C*01:01:01, who were taking the lowest doses. The highest dose of tacrolimus (TAC) was administered to patients with alleles A*68:01:02, A*29:01:01, B*07:02:01, B*35:02:01, B*38:01:01, DRB1*12:01:01, DQB1*05:03:01, or haplotypic variations A*02:01:01-B*57:01:01-C*07:01:01, A*03:01:01-B*07:02:01-C*13:01:01, A*29:02:01-B*44:03:01- C*07:01:01, and A*01:01:01-B*08:01:01-C*03:01:01. Additionally, it was established that HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DPA1, and HLA-DQA1 show very slight polymorphism, which suggests that there is no need for their typing for transplantation purposes. Moreover, loci HLA-C, HLA-DQB1, and HLA-DPB1, which are not routinely examined in recipient-donor matching, show genetic variability that may increase the risk of transplant rejection or shortened graft life. CONCLUSIONS: Expanding the qualification procedure to include allele genotyping could allow clinicians to establish immunosuppressive treatment schemes that would be optimally suited for recipients' phenotype.

Factors Influencing Long-Term Survival of Kidney Grafts Transplanted From Deceased Donors-Analysis Based on a Single-Center Experience.

BACKGROUND: Kidney transplantation is a routine procedure in the treatment of patients with kidney failure and requires collaboration of experts from different disciplines. Improvements in the procedure result from numerous factors. METHODS: The analyzed group consisted of 150 patients divided into 2 equal subgroups: long-term (>15 years) and short-term (<6 years) graft survival. The following factors were taken into consideration: graft survival time, HLA mismatches, recipient sex, sex compatibility, panel reactive antibodies (PRA), cold ischemia time (CIT), and cause of kidney insufficiency. Factors were analyzed in groups with the use of Student t and chi-square tests, Kruskal-Wallis analysis of variance (ANOVA), and multifactorial ANOVA. RESULTS: Basic statistical analysis revealed no significance between long-term and short-term survival groups in HLA mismatches, recipient sex, or sex compatibility. There was a very significant difference in CIT. ANOVA revealed no statistical difference between groups in recipient sex, sex compatibility, or recipient disease. There were more patients in the group with long-term survival with lower PRA. There were more women in the group with long-term survival who received kidneys from men. Multifactorial analysis revealed no interactions or independent influence of the selected factors. CONCLUSIONS: CIT was a strong independent factor influencing graft survival. Recipient sex and cause of kidney insufficiency seemed to have no impact. Lower PRA was positively correlated with long-term survival. Women who received kidneys from men lived longer with functioning grafts.

A hedgehog pathway-dependent gene signature is associated with poor clinical outcomes in Luminal A breast cancer.

PURPOSE: High expression of glioma-associated oncogene homolog-1 (GLI1) is associated with poor prognosis in estrogen receptor (ER) positive breast cancers. We sought to define a GLI1-dependent gene signature in ER-positive tumors that could further stratify patients at higher risk for disease recurrence and potentially lead to novel combination therapies. METHODS: We identified an inverse correlation between GLI1 expression and distant disease-free survival (DFS) using a dataset developed at MD Anderson Cancer Center (Hatzis dataset) containing clinical data from 508 breast cancer patients. Using a qPCR-based microarray platform, we identified genes differentially regulated by GLI1 in MCF7 cells and then determined if expression of these genes correlated with GLI1 expression in patient tumor samples. Statistical comparison between the groups was performed by ANOVA. Direct comparison of two groups was done by a two-tailed t test. Correlations between variables were done by Pearson's method. RESULTS: Expression of GLI1 and its target genes correlated significantly with worse distant DFS in breast cancer patients with Luminal A molecular subtype. Particularly, co-expression of GLI1 with EGFR and/or SNAI1, two of the identified GLI1 targets, was predictive of worse distant DFS in this subtype. Furthermore, patients with Luminal A tumors with a high GLI1 signature had a shorter distant DFS compared to the Luminal B subtype and the outcome for this group was comparable to patients with HER2-positive or basal-like tumors. CONCLUSION: We have identified a novel GLI1 gene signature that is associated with worse clinical outcomes among the patients with Luminal A subtype of breast cancer.

Stromal PTEN inhibits the expansion of mammary epithelial stem cells through Jagged-1.

This corrects the article DOI: 10.1038/onc.2016.383.

Effect of Lactobacillus on body weight and body fat in overweight subjects: a systematic review of randomized controlled clinical trials.

Gut microbiota is important for maintaining body weight. Modulation of gut microbiota by probiotics may result in weight loss and thus help in obesity treatment. The aim of this systematic review was to evaluate the effects of Lactobacillus on weight loss and/or fat mass in overweight adults. A search was performed on the Medline (PubMed) and Scopus electronic databases using the search terms: 'probiotics', 'Lactobacillus, 'obesity', 'body weight changes', 'weight loss', 'overweight', 'abdominal obesity', 'body composition', 'body weight', 'body fat' and 'fat mass'. In the total were found 1567 articles, but only 14 were included in this systematic review. Of these nine showed decreased body weight and/or body fat, three did not find effect and two showed weight gain. Results suggest that the beneficial effects are strain dependent. It can highlight that Lactobacillus plantarum and Lactobacillus rhamnosus when combined with a hypocaloric diet, L. plantarum with Lactobacillus curvatus, Lactobacillus gasseri, Lactobacillus amylovorus, Lactobacillus acidophilus and Lactobacillus casei with phenolic compounds, and multiple species of Lactobacillus.

Stromal PTEN inhibits the expansion of mammary epithelial stem cells through Jagged-1.

Fibroblasts within the mammary tumor microenvironment are active participants in carcinogenesis mediating both tumor initiation and progression. Our group has previously demonstrated that genetic loss of phosphatase and tensin homolog (PTEN) in mammary fibroblasts induces an oncogenic secretome that remodels the extracellular milieu accelerating ErbB2-driven mammary tumor progression. While these prior studies highlighted a tumor suppressive role for stromal PTEN, how the adjacent normal epithelium transforms in response to PTEN loss was not previously addressed. To identify these early events, we have evaluated both phenotypic and genetic changes within the pre-neoplastic mammary epithelium of mice with and without stromal PTEN expression. We report that fibroblast-specific PTEN deletion greatly restricts mammary ductal elongation and induces aberrant alveolar side-branching. These mice concomitantly exhibit an expansion of the mammary epithelial stem cell (MaSC) enriched basal/myoepithelial population and an increase in in vitro stem cell activity. Further analysis revealed that NOTCH signaling, specifically through NOTCH3, is diminished in these cells. Mechanistically, JAGGED-1, a transmembrane ligand for the NOTCH receptor, is downregulated in the PTEN-null fibroblasts leading to a loss in the paracrine activation of NOTCH signaling from the surrounding stroma. Reintroduction of JAGGED-1 expression within the PTEN-null fibroblasts was sufficient to abrogate the observed increase in colony forming activity implying a direct role for stromal JAGGED-1 in regulation of MaSC properties. Importantly, breast cancer patients whose tumors express both low stromal JAG1 and low stromal PTEN exhibit a shorter time to recurrence than those whose tumors express low levels of either alone suggesting similar stromal signaling in advanced disease. Combined, these results unveil a novel stromal PTEN-to-JAGGED-1 axis in maintaining the MaSC niche, and subsequently inhibiting breast cancer initiation and disease progression.

Prostate Specific Antigen-Positive Deceased Organ Donor: A Pathologist Is Indispensable.

BACKGROUND: Due to demographic projections, and lack of an algorithm in the case of a prostate specific antigen (PSA)-positive donor, the loss of organ recovery may occur more frequently in the near future without approved procedures. In Poland in recent years it has been recommended to determine tumor markers in potential donors. In the first year of the recommendation 10% of potential deceased donors were disqualified in our transplantation center on the basis of the elevated PSA levels (high PSA >10 ng/mL). Histopathologic evaluation of prostate was implemented in a donor qualification procedure to prevent reduction of the actual organ donor pool. MATERIAL AND METHODS: In the period of January 2010-January 2014 each donor reported to a coordination center (n = 52; median age, 54 years) and underwent the routine histological evaluation of the whole prostate, regardless of the PSA level. RESULTS: Pathologist revealed in the study group of 52 male donors, 6 cases of carcinoma of the prostate (CaP; 12%). There was no correlation between PSA level and CaP (-)/CaP(+) (median 7.0 vs 3.9 ng/mL, respectively; P = .51) nor high-grade prostate intraepithelial neoplasia (HGPIN) (+)/HGPIN (-) (median 5.9 vs 4.3 ng/mL; P = .14). All of the recovered organs (12 kidneys and 3 livers) from donors with CaP were transplanted, resulting in a 15% increase in the organ donor pool. CONCLUSIONS: There is no association between PSA values and CaP occurrence in deceased organ donors. Histological verification allowed for an increase in the organ pool with maintenance of safety standards.

Prostate-Specific Antigen: Nonspecific in Deceased Organ Donors.

Currently, there is no clear position regarding the donation of organs from donors with prostate carcinoma (CaP) in European countries, except Italy. The lengthening of life expectancy increases the probability of prostate cancer among potential organ donors. The concentration of prostate-specific antigen (PSA) >2 ng/mL at 60 years of age is related to the increasing possibility of identifying an advanced form of CaP. In recent years in Poland, the recommendation has been to determine tumor markers in potential donors. In the first year of the recommendation, 10% of potential male cadaveric donors were disqualified in West Pomerania, Poland, on the basis of elevated PSA levels (>10 ng/mL). To avoid reduction of the actual donor pool, each potential male donor reported to the center since January 2010 undergoes a routine histologic evaluation of the whole prostate, regardless of the PSA level, before organ implantation. In the study group (N = 52), histopathologic evaluation revealed 6 cases of CaP (12%). In CaP positive group Gleason score range from 2+2 to 3+4. In CaP donors PSA level have been noticed in range 1.79 ng/mL - 7.66 ng/mL. There was no correlation between histologically confirmed CaP and the PSA level.

Boolean network identification from perturbation time series data combining dynamics abstraction and logic programming.

Boolean networks (and more general logic models) are useful frameworks to study signal transduction across multiple pathways. Logic models can be learned from a prior knowledge network structure and multiplex phosphoproteomics data. However, most efficient and scalable training methods focus on the comparison of two time-points and assume that the system has reached an early steady state. In this paper, we generalize such a learning procedure to take into account the time series traces of phosphoproteomics data in order to discriminate Boolean networks according to their transient dynamics. To that end, we identify a necessary condition that must be satisfied by the dynamics of a Boolean network to be consistent with a discretized time series trace. Based on this condition, we use Answer Set Programming to compute an over-approximation of the set of Boolean networks which fit best with experimental data and provide the corresponding encodings. Combined with model-checking approaches, we end up with a global learning algorithm. Our approach is able to learn logic models with a true positive rate higher than 78% in two case studies of mammalian signaling networks; for a larger case study, our method provides optimal answers after 7min of computation. We quantified the gain in our method predictions precision compared to learning approaches based on static data. Finally, as an application, our method proposes erroneous time-points in the time series data with respect to the optimal learned logic models.

Expression of neurotrophins and their receptors in human CD34+ bone marrow cells.

Bone marrow (BM) CD34+ cells have the ability to secrete growth factors, cytokines, and chemotactic factors. We sought to better characterize this population and to investigate whether human BM CD34+ cells express neurotrophins (NTs) and their relevant receptors. We also compared their expression levels with BM nucleated cells (NCs). BM CD34+ cells were evaluated with respect to the expression levels of neurotrophins using qRT-PCR, immunofluorescent staining, and Western blotting. Next, the expression of specific (TrkA, TrkB, TrkC) and non-specific (p75NTR) neurotrophin receptors was detected by qRT-PCR and immunofluorescent staining in BM CD34+ cells. Using qRT- PCR, we show that even in the absence of inducing factors, CD34+ cells spontaneously express neurotrophins such as NGF, BDNF, NT-3, and NT-4. In addition, the NT expression levels in BM CD34+ cells are considerably higher than in NCs. Furthermore, we confirmed intracellular NT expression in BM CD34+ cells at the protein level using immunofluorescent staining and Western blotting. Using qRT-PCR, we found that immunomagnetically separated BM CD34+ cells spontaneously express high-affinity neurotrophin receptors (TrkA, TrkB, and TrkC) and the low-affinity receptor p75NTR at higher levels than NCs. Immunomagnetic CD34+ cell separation enables for the rapid and gentle sorting of stem/progenitor cells (SPCs) to prepare specific cell types for use in research and clinical applications. Our study suggests that BM CD34+ cells have the potential to support trophic factors for neural tissue and could contribute towards the protection and regeneration of neural cells.

The influence of the tumor necrosis factor-alpa-308G>A polymorphism on the efficacy of immunosuppressive therapy in patients after kidney transplantation.

Cytokines play an important role in the immune response. The calcineurin inhibitors (cyclosporine CsA, tacrolimus TAC) widely used after renal transplantation to prevent allograft rejection are immunosuppressive drugs suppressing the production of cytokines. These drugs are characterized by interindividual variability and require monitoring their blood concentrations to predict their optimal dosage. Therefore, the aim of the study was to determine the correlation between therapeutic effects of immunosuppressants and the tumor necrosis factor-α (TNF-α)-308G>A polymorphism in renal transplant patients. A total of 412 patients receiving TAC and CsA were included in the study. Genotype frequencies were determined using the real-time PCR method. Patients with the GG genotype received higher doses of TAC as compared to carriers of the GA genotype (5.24 mg versus 3.35 mg) and had lower mean drug concentration in blood (5.86 ng/ml versus 6.92 ng/ml). Similar results were also obtained for CsA (GG: 185.33 mg versus GA: 153.30 mg, P < 0.05). The comparison of the TNF-α-308G>A polymorphism with the biochemical parameters did not reveal a potential risk for transplant rejection. These results indicate that the TNF-α-308G>A polymorphism may influence the dosage of immunosuppressive drugs in patients after transplantation as far as individualization of drug therapy is concerned.

New injectable elastomeric biomaterials for hernia repair and their biocompatibility.

Complications associated with implantation of polymeric hernia meshes remain a difficult surgical challenge. We report here on our work, developing for the first time, an injectable viscous material that can be converted to a solid and elastic implant in vivo, thus successfully closing herniated tissue. In this study, long-chain fatty acids were used for the preparation of telechelic macromonomers end-capped with methacrylic functionalities to provide UV curable systems possessing high biocompatibility, good mechanical strength and flexibility. Two different systems, comprising urethane and ester bonds, were synthesized from non-toxic raw materials and then subjected to UV curing after injection of viscous material into the cavity at the abdominal wall during hernioplasty in a rabbit hernia model. No additional fixation or sutures were required. The control group of animals was treated with commercially available polypropylene hernia mesh. The observation period lasted for 28 days. We show here that artificially fabricated defect was healed and no reherniation was observed in the case of the fatty acid derived materials. Importantly, the number of inflammatory cells found in the surrounding tissue was comparable to these found around the standard polypropylene mesh. No inflammatory cells were detected in connective tissues and no sign of necrosis has been observed. Collectively, our results demonstrated that new injectable and photocurable systems can be used for minimally invasive surgical protocols in repair of small hernia defects.

Identification of preferential CD4+ T-cell targets for HIV infection in the cervix.

A better understanding of the cellular targets of HIV infection in the female genital tract may inform HIV prevention efforts. Proposed correlates of cellular susceptibility include the HIV co-receptor CCR5, peripheral homing integrins, and immune activation. We used a CCR5-tropic pseudovirus to quantify HIV entry into unstimulated endocervical CD4(+) T cells collected by cytobrush. Virus entry was threefold higher into cervix-derived CD4(+) T cells than blood, but was strongly correlated between these two compartments. Cervix-derived CD4(+) T cells expressing CD69, α(4)ß(7), or α(4)ß(1) were preferential HIV targets; this enhanced susceptibility was strongly correlated with increased CCR5 expression in α(4)ß(7)(+) and CD69(+) CD4(+) T cells, and to a lesser extent in α(4)ß(1)(+) CD4(+) T cells. Direct binding of gp140 to integrins was not observed, integrin inhibitors had no effect on virus entry, and pseudotypes with an env that preferentially binds α(4)ß(7) still demonstrated enhanced entry into α(4)ß(1)(+) cells. In summary, a rapid and sensitive HIV entry assay demonstrated enhanced susceptibility of activated endocervical CD4(+) T cells, and those expressing α(4)ß(7) or α(4)ß(1). This may relate to increased CCR5 expression by these cell subsets, but did not appear to be due to direct interaction of α(4)ß(7) or α(4)ß(1) with HIV envelope.

E2f3 in tumor macrophages promotes lung metastasis.

The Rb-E2F axis is an important pathway involved in cell-cycle control that is deregulated in a number of cancers. E2f transcription factors have distinct roles in the control of cell proliferation, cell survival and differentiation in a variety of tissues. We have previously shown that E2fs are important downstream targets of a CSF-1 signaling cascade involved in myeloid development. In cancer, tumor-associated macrophages (TAMs) are recruited to the tumor stroma in response to cytokines secreted by tumor cells, and are believed to facilitate tumor cell invasion and metastasis. Using the MMTV-Polyoma Middle T antigen (PyMT) mouse model of human ductal carcinoma, we show that the specific ablation of E2f3 in TAMs, but not in tumor epithelial cells, attenuates lung metastasis without affecting primary tumor growth. Histological analysis and gene expression profiling suggest that E2f3 does not impact the proliferation or survival of TAMs, but rather controls a novel gene expression signature associated with cytoskeleton rearrangements, cell migration and adhesion. This E2f3 TAM gene expression signature was sufficient to predict cancer recurrence and overall survival of estrogen receptor (ER)-positive breast cancer patients. Interestingly, we find that E2f3b but not E2f3a levels are elevated in TAMs from PyMT mammary glands relative to controls, suggesting a differential role for these isoforms in metastasis. In summary, these findings identify E2f3 as a key transcription factor in TAMs, which influences the tumor microenvironment and tumor cell metastasis.