Niches In Organs Research Articles

Comprehensive analysis and assessment of the production and export potential of organic niche products

The object of the study is the determination of ecological and economic efficiency in relation to the production of organic niche products. The strategic perspective of the production and export of organic niche products in Ukraine is considered as one of the ways to overcome economic challenges exacerbated by global instability and geopolitical tensions. The production of organic products is outlined as a strategically important direction of the country's agricultural sector, which has significant export potential, especially to the countries of the European Union, where there is a steady increase in demand for organic products. A comprehensive approach to strategy implementation is proposed, which includes market research, production development, marketing and branding, as well as optimization of logistics and export processes. The dynamics of the main indicators of the development of organic agriculture in Ukraine from 2010–2021, the volume of imports of organic products to the countries of the European Union by exporting countries were analyzed. To date, only 1 % of agricultural crops are «eco», the volume of organic products has significantly increased, and the yield of organic products has increased by 5–20 % with a corresponding reduction in material costs. Since the end of the 1990s, the agricultural sector of Ukraine began to focus intensively on organic production, taking into account the growing global trend towards the sustainable development of the agro-industrial complex, etc. Given their uniqueness, growing niche crops can offer advantages such as minimal competition and the potential for significant profits, especially when the products find widespread use. A comparative analysis of the production of organic products on the domestic and foreign markets of Ukraine was conducted. A SWOT analysis of the production of organic products in Ukraine was developed to determine the strengths and weaknesses. The practical value is providing advice to producers on growing niche crops, creating market demand, attracting foreign partners to implement such projects in Ukraine, which will contribute to strengthening the economic potential of agricultural producers. This will help increase the competitiveness of domestic enterprises in the local and global markets, make them more resistant to economic challenges and help reduce risks, etc.

Anticancer Therapy Targeting Cancer-Derived Extracellular Vesicles.

Extracellular vesicles (EVs) are natural lipid nanoparticles secreted by most types of cells. In malignant cancer, EVs derived from cancer cells contribute to its progression and metastasis by facilitating tumor growth and invasion, interfering with anticancer immunity, and establishing premetastasis niches in distant organs. In recent years, multiple strategies targeting cancer-derived EVs have been proposed to improve cancer patient outcomes, including inhibiting EV generation, disrupting EVs during trafficking, and blocking EV uptake by recipient cells. Developments in EV engineering also show promising results in harnessing cancer-derived EVs as anticancer agents. Here, we summarize the current understanding of the origin and functions of cancer-derived EVs and review the recent progress in anticancer therapy targeting these EVs.

Basic and additional ecological niches of soil phytopatogenes on spring wheat varieties in West Siberia

The elucidation of hydrothermal and temporal parameters of the realization of the main and additional ecological niches of jointly parasitizing widespread soil phytopathogenic micromycetes has theoretical and applied significance. The aim of the study was to identify the parameters of the implementation of the main and additional ecological niches by the dominant species of soil micromycetes on spring wheat (Bipolaris sorokiniana Sacc. Shoem., Fusarium poae (Peck.) Wollenw., F. oxysporum Schltdl.) in the system of underground and generative organs of spring wheat varieties. The objectives of the study included determining the level of realization of the main ecological niches by three dominant species of soil pathogenic micromycetes in the system of underground organs of spring wheat varieties in different phases of vegetation, as well as identifying the degree of realization by micromycetes of additional ecological niches in generative organs of spring wheat varieties and assessing the strength of the influence of varieties and conditions of the year on the size of ecological niches in underground and generative organs of plants. The study was conducted on 20 varieties of spring wheat in 2020–2022, in the northern forest-steppe of the Ob region according to generally accepted and author’s methods. It is shown that the soil micromycetes B. sorokiniana, Fusarium poae and F. oxysporum, parasitizing together on the underground and generative organs of spring wheat, have different hydrothermal and temporal parameters of the realization of the main and additional ecological niches. B. sorokiniana is a relatively thermophilic species, its parasitic activity is most successful in underground, especially straw organs, is realized in conditions of unstable humidification, F. poae is a moisture-loving micromycete that prefers underground, especially young organs of spring wheat plants, F. oxysporum is a drought-resistant species that tends to more mature plant organs. As for the generative organs of wheat, B. sorokiniana colonizes them by airborne droplets in humid conditions, keeping them confined to straw-like tissues, the correlation coefficient of B. sorokiniana infection of the ear rods and the SCC of August was equal to r = 0.812 ± 0.412. F. poae could reach ears by vessels, the degree of their colonization by this micromycete was small and practically did not depend on the weather conditions of the year and its representation in underground plant organs. F. oxysporum colonized ears of spring wheat by vessels, and the degree of its representation in pathocomplexes of generative organs closely correlated with its share in pathocomplexes of primary and secondary roots: r = 0.923 ± 0.146.

SAT041 18F-FDG PET/CT Mapping Of Functional Microbial Niches To Understand Host Glucose Regulation After BCG Vaccinations

Abstract Disclosure: H. Dias: None. J.F. Fu: None. T.G. Luck: None. G.E. Wolfe: None. E. Hostetter: None. N.C. Ng: None. H. Zheng: None. W. Kühtreiber: None. J.C. Price: None. C. Catana: None. D.L. Faustman: None. Diverse microbiomes in humans are known to change host energy metabolism. When the bacillus Calmette-Guérin (BCG) vaccine, which consists of live but avirulent Mycobacterium bovis, is introduced as experimental therapy into human hosts with underlying type 1 diabetes (T1D), the BCG bacillus has been shown to gradually shift energy metabolism in host blood lymphoid cells from oxidative phosphorylation to aerobic glycolysis. Aerobic glycolysis draws more glucose out of the blood to fuel intracellular metabolism, and it may underlie the BCG bacillus’ therapeutic benefit: the systemic and long-term reduction of excess glucose from the blood of TID patients. The organ-specific niches where the BCG bacillus similarly alters metabolism and establishes persistent residence are not known. In a human clinical trial, we mapped the organ(s) niches for BCG-induced shift to aerobic glycolysis using fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and x-ray computed tomography (CT). This technique allowed us to reveal quantitatively, by Standardized Uptake Value Ratios, the organs with heightened glucose uptake in T1D participants (n=6) over a 2-year time-period after BCG vaccination versus before vaccination, as well as confirm earlier work that BCG vaccination gradually lowers blood sugar levels without any contribution from endogenous insulin. We also tested BALB/c mice (n=17) for the direct presence of BCG colonies in particular organ niches before and after vaccination. Results from both human and murine studies of the BCG microorganism concurred that the major anatomic site of functional metabolic change and residence is the spleen. The BCG bacillus also transiently mapped to the bone marrow, liver, circulating lymphocytes as in the descending aorta, and the lungs. Findings from human and murine studies support the spleen as the niche for the BCG vaccine’s functional improvement of metabolism. The spleen is significant because it is a lymphoid organ massive enough to explain BCG’s systemic benefit of lowering blood sugar to near normal levels in T1D. Presentation: Saturday, June 17, 2023

The Competitiveness of Ethiopian Honey in the European Union and the United Kingdom

In spite of efforts made by the government, to help the private sector, Ethiopia remains one of the poorest countries in Africa. The agri-food sector provides 75% of jobs in Ethiopia (United States Agency for International Development, 2023). However, most agriculture products are sold unprocessed and undifferentiated. Ethiopia is regarded as a country of high potential for honey and beeswax production. Ethiopian honey production is estimated at 45,000 tonnes, however, the country is only exporting 800 tonnes (Alemu & Adesina, 2015). Some of the most promising destinations for Ethiopian honey exports include the European Union (EU) and the United Kingdom (UK). Within this context, this paper aims to critically analyse the competitiveness of the Ethiopian honey value chain in order to identify its challenges and opportunities within the EU and UK market. This study uses a qualitative research approach. Primary data were collected from stakeholders of the Ethiopian honey value chain. The results of this study indicate that Ethiopian honey could be competitive in the specialty and organic niche market. Findings have revealed that the Ethiopian honey value chain needs improvement in terms of quality, food safety, market information management and cooperation among stakeholders. The findings of this research make a contribution to the existing literature by extending current knowledge within this domain and identifying strategies to penetrate a very competitive sector.

Dynamic crosstalk between hematopoietic stem cells and their niche from emergence to aging.

The behavior of somatic stem cells is regulated by their niche. Interaction between hematopoietic stem cells (HSCs) and their niches are a representative model to understand stem cell-niche interplay. Here, we provide an overview of crosstalk between HSCs and their niches in bone marrow and extramedullary organs following the life journey of HSCs from emergence, development, maturation until aging. We highlight the unique differences of HSC niches in different life stages within various organs focusing on recent literature to propose new speculations and hypotheses.

Abstract B019: Identify features of fibroblast and macrophage which regulate metastasis of triple-negative breast cancer

Abstract The tumor microenvironment (TME), which the cancer is known to remodel, can interact with cancer in various ways, such as promoting or hindering metastasis. The challenge with comprehending TME is that each patient's individual variance makes it difficult to carry out a consistent analysis. We used the PDX model to analyze the alterations entirely brought about by cancer cells of each patient in the same environment exclusively. In 121 breast cancer patients, we created a PDX model and performed WES and RNA-seq. We repeatedly performed metastatic induction tests on the models of 26 TNBC patients among the PDX models we generated. The replicated experiments confirmed that cancer cells with frequent metastasis usually spread well, while cancer cells with seldom metastases rarely metastasize. For each of the five samples that had the greatest and worst rates of metastasis, the pre-metastatic xenograft tumor was analyzed using scRNA-seq. Metastasis could not be predicted by only cancer cells because there was no difference between the two groups. Still, fibroblasts and macrophages had distinct gene markers before metastasis which can predict metastasis. To explore TME that develops pre-metastatic niches (PMN) in organs that would be metastasis targets, we developed a metastatic model using 4T1 cell lines. Daily lung macrophage RNA-seq, lung WES, and lung scRNA-seq procedures were carried out for four weeks to examine the precise timing of metastasis and the daily changes in the transcriptome. Surprisingly, a few days before the presence of any cancer cells, the gene expression of lung macrophages had already undergone significant modification. Additionally, only injections of tumor-conditioned media that mimicked metastasis could activate PMN in lung macrophages. Citation Format: Woochan Lee, Hyewon Chung, Woohang Heo, Hyeong-Gon Moon, Seung Hyeok Seok, Jong-Il Kim. Identify features of fibroblast and macrophage which regulate metastasis of triple-negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr B019.

Role of myeloid-derived suppressor cells in tumor recurrence.

The establishment of primary tumor cells in distant organs, termed metastasis, is the principal cause of cancer mortality and is a crucial therapeutic target in oncology. Thus, it is critical to establish a better understanding of metastatic progression for the future development of improved therapeutic approaches. Indeed, such development requires insight into the timing of tumor cell dissemination and seeding of distant organs resulting in occult lesions. Following dissemination of tumor cells from the primary tumor, they can reside in niches in distant organs for years or decades, following which they can emerge as an overt metastasis. This timeline of metastatic dormancy is regulated by interactions between the tumor, its microenvironment, angiogenesis, and tumor antigen-specific T-cell responses. An improved understanding of the mechanisms and interactions responsible for immune evasion and tumor cell release from dormancy would help identify and aid in the development of novel targeted therapeutics. One such mediator of dormancy is myeloid derived suppressor cells (MDSC), whose number in the peripheral blood (PB) or infiltrating tumors has been associated with cancer stage, grade, patient survival, and metastasis in a broad range of tumor pathologies. Thus, extensive studies have revealed a role for MDSCs in tumor escape from adoptive and innate immune responses, facilitating tumor progression and metastasis; however, few studies have considered their role in dormancy. We have posited that MDSCs may regulate disseminated tumor cells resulting in resurgence of senescent tumor cells. In this review, we discuss clinical studies that address mechanisms of tumor recurrence including from dormancy, the role of MDSCs in their escape from dormancy during recurrence, the development of occult metastases, and the potential for MDSC inhibition as an approach to prolong the survival of patients with advanced malignancies. We stress that assessing the impact of therapies on MDSCs versus other cellular targets is challenging within the multimodality interventions required clinically.

Pathways of Transition to Organic Agriculture in Morocco

Agriculture is a vital sector in Morocco through its contribution to the gross domestic product (13%) and workforce (30%). However, the sector faces important sustainability challenges due to Morocco’s dependence on rain-fed crops for 90% of the production and its vulnerability to climate change. In this context, organic agriculture presents itself as a promising alternative to valorize production and mitigate climate change effects. This article describes the dynamics and development of the organic agriculture niche in Morocco through the lens of the Multi-Level Perspective (MLP) on socio-technical transitions. The MLP is a widely used framework that bases its analysis on transitions being the result of the interaction of niches, socio-technical regimes, and socio-technical landscape. Results of the literature review and semi-structured interviews show that, although the organic niche is relatively well established (11,000 ha of organic land area in 2019), it is still developing at a slower rate than expected due to multiple setbacks. While organic farming does solve many sustainability challenges that Moroccan agriculture faces, it still lacks the infrastructure and human capital to succeed as a niche. All in all, organic farming is still in the first transition stages and can follow a multitude of pathways before becoming relevant in the current agri-food system.

Abstract 6000: A millifluidic culture platform for quantifying premetastatic niche cultivation in quiescent organ stroma induced by real-time transport of tumor-derived factors

Abstract Progression to metastasis contributes to the poor overall survival of patients diagnosed with aggressive cancers such as triple negative breast cancer (TNBC). Tumor-derived factors (TDF) induce pathological changes in distant organ niches that render these organs more receptive to colonization by disseminated tumor cells. This process, termed premetastatic niche (PMN) cultivation, is characterized in part by pathological activation of stromal cells and induction acute extracellular matrix (ECM) deposition. There is an urgent and unmet need for models of PMN cultivation in human cancers to accelerate the discovery of mechanisms and develop PMN-targeting therapies. We engineered 3D culture models of aggressive carcinoma and quiescent organ interstitium and integrated them in a millifluidic device that enables interconnected coculture. Our devices are engineered for ease of adoption by labs with experience culturing cells and organoids in 3D hydrogels. Cultures can be performed in static, with continuous gravity-driven flow, or with a rocker for recirculating flow. Here we present a form of the model in which a patient-derived triple negative breast cancer microenvironment is linked with a quiescent lung interstitium. Fibroblast activation and ECM synthesis indicative of PMN cultivation are quantified relative to a physiological resting state. All device cultures were maintained with fibroblast growth medium containing 0.1% FBS and 1% ITS which maintains the lung compartment in a quiescent state in the absence of endogenous activating factors in the system. The TME compartment in our devices exhibited features of aggressive cancers after 7 days of culture including widespread 3D invasion of tumor cells and formation of a dense stroma comprised of myofibroblast-like CAF with prominent smooth muscle actin (SMA) cytoskeleton and nuclear translocation of activated Yes-associated protein 1 (aYAP1). These cellular features of the engineered tumor microenvironment were accompanied by a dense anisotropic matrix of newly-synthesized fibronectin. TNBC-derived factors transported in the system induced PMN cultivation in the lung compartment by 7 days, as evidenced by quantitative increases in focal deposition of fibronectin and a spectrum of activated phenotypes defined by SMA and aYAP1 expression patterns in previously quiescent fibroblasts. Thus, we have captured cancer-induced changes in the density and architecture of newly-synthesized ECM in a distant tissue that would support tumor cell adhesion. Citation Format: Elisabet A. Olsen, Omar M. Ahmad, Bradley Sweeney, Caroline C. Culp, Yasmin V. Maurice, Matthew R. Burow, Mark Mondrinos. A millifluidic culture platform for quantifying premetastatic niche cultivation in quiescent organ stroma induced by real-time transport of tumor-derived factors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6000.

The theory of tumor ecosystem.

Cancer cells can be conceived as “living organisms” interacting with cellular or non‐cellular components in the host internal environment, not only the local tumor microenvironment but also the distant organ niches, as well as the immune, nervous and endocrine systems, to construct a self‐sustainable tumor ecosystem. With increasing evidence for the systemic tumor‐host interplay, we predict that a new era of cancer therapy targeting the ecosystemic vulnerability of human malignancies has come. Revolving around the tumor ecosystem scoped as different hierarchies of primary, regional, distal and systemic onco‐spheres, we comprehensively review the tumor‐host interaction among cancer cells and their local microenvironment, distant organ niches, immune, nervous and endocrine systems, highlighting material and energy flow with tumor ecological homeostasis as an internal driving force. We also substantiate the knowledge of visualizing, modelling and subtyping this dynamically intertwined network with recent technological advances, and discuss ecologically rational strategies for more effective cancer therapies.

A glitch in the matrix: organ-specific matrisomes in metastatic niches.

Modification of the extracellular matrix (ECM) is a critical aspect of developing a metastasis-supportive organ niche. Recent work investigating ECM changes that facilitate metastasis has revealed ways in which different metastatic organ niches are similar as well as the distinct characteristics that make them unique. In this review, we present recent findings regarding how ECM modifications support metastasis in four frequent metastatic sites: the lung, liver, bone, and brain. We discuss ways in which these modifications are shared between metastatic organs as well as features specific to each location. We also discuss areas of technical innovation that could be advantageous to future research and areas of inquiry that merit further investigation.

Pancreatic Cancer Small Extracellular Vesicles (Exosomes): A Tale of Short- and Long-Distance Communication.

Simple SummaryEven today, pancreatic cancer still has a dismal prognosis. It is characterized by a lack of early symptoms and thus late diagnosis as well as early metastasis. The majority of patients suffer from pancreatic ductal adenocarcinoma (PDAC). PDACs communicate extensively with cellular components of their microenvironment, but also with distant metastatic niches to facilitate tumor progression and dissemination. This crosstalk is substantially enabled by small extracellular vesicles (sEVs, exosomes) with a size of 30–150 nm that are released from the tumor cells. sEVs carry bioactive cargos that reprogram target cells to promote tumor growth, migration, metastasis, immune evasion, or chemotherapy resistance. Interestingly, sEVs also carry novel diagnostic, prognostic and potentially also predictive biomarkers. Moreover, engineered sEVs may be utilized as therapeutic agents, improving treatment options. The role of sEVs for PDAC development, progression, diagnosis, prognosis, and treatment is the focus of this review.Even with all recent advances in cancer therapy, pancreatic cancer still has a dismal 5-year survival rate of less than 7%. The most prevalent tumor subtype is pancreatic ductal adenocarcinoma (PDAC). PDACs display an extensive crosstalk with their tumor microenvironment (TME), e.g., pancreatic stellate cells, but also immune cells to regulate tumor growth, immune evasion, and metastasis. In addition to crosstalk in the local TME, PDACs were shown to induce the formation of pre-metastatic niches in different organs. Recent advances have attributed many of these interactions to intercellular communication by small extracellular vesicles (sEVs, exosomes). These nanovesicles are derived of endo-lysosomal structures (multivesicular bodies) with a size range of 30–150 nm. sEVs carry various bioactive cargos, such as proteins, lipids, DNA, mRNA, or miRNAs and act in an autocrine or paracrine fashion to educate recipient cells. In addition to tumor formation, progression, and metastasis, sEVs were described as potent biomarker platforms for diagnosis and prognosis of PDAC. Advances in sEV engineering have further indicated that sEVs might once be used as effective drug carriers. Thus, extensive sEV-based communication and applications as platform for biomarker analysis or vehicles for treatment suggest a major impact of sEVs in future PDAC research.

Expression and antimicrobial activity of liver-expressed antimicrobial peptides in the ovaries of the viviparous teleost Xenotoca eiseni

The mechanism via which the mothers of viviparous animals regulate the internal environment of pregnancy-associated organs for maintaining offspring growth is poorly understood. Environmental niches in organs contain fluid components for supporting embryonic growth; however, they may serve as nutrients for microbes. Therefore, microbial control is essential in viviparous animals to reduce the risk of infection in the ovarian lumen. Its importance may be higher than that in the case of oviparous animals. In this study, we investigated the antimicrobial factors in a viviparous teleost, Xenotoca eiseni. Four transcripts of the liver-expressed antimicrobial peptide (LEAP) were identified via RNA-Seq analysis. Some of the genes were expressed in the ovaries or intraovarian embryos of the fish. In particular, high expression of leap1a was detected in the ovaries of both pregnant and non-pregnant fish. Moreover, the ovary extracts from X. eiseni and transformed leap genes exhibited antimicrobial activity against Escherichia coli. Our results suggest that viviparous teleosts utilize antimicrobial peptides to reduce the risk of infection in the ovarian lumen.

TRANSITION TO ORGANIC AGRICULTURE IN MOROCCO

Agriculture is a vital sector in Morocco; it contributes 13% to the gross domestic product and employs around 30% of the total workforce and 70% in the rural areas. This puts agriculture in a sensitive spot where it affects the livelihoods of a great proportion of the population. Moroccan agricultural development programs (viz. Green Morocco Plan 2008-2019 and Green Generation 2020-2030) aim to enhance the livelihoods of farmers by focusing on the valorisation of small farms and rural areas through the development of protected geographic indications (PGI), cooperatives, and organic farming. This review paper describes the dynamics and development process of the organic agriculture niche in Morocco through the lens of the Multi-Level Perspective (MLP) on socio-technical transitions. The MLP is a widely used framework that bases its analysis on transitions being the result of the interaction of niches, socio-technical regimes, and socio-technical landscape. Niches represent novelties, regimes are the incumbent and dominant systems, and the landscape includes the external factors that affect both regimes and niches and shape their development. Results show that although the organic niche is well established (11,000 ha of organic land area in 2019), it is still developing at a slower rate than expected. While organic farming does solve many sustainability challenges that Moroccan agriculture faces, it still lacks the infrastructure and human capital to succeed as a niche. All in all, organic farming is still in the first transition stages and can follow a multitude of pathways before becoming relevant in the current agri-food system.

Neuroeconomic Decisions in Cocoa Producers: Impact of Cooperative Innovation Methodology on Prospecting for Fair Trade Organic Niche as an Incentive for Agricultural Sustainability

This article focuses on analyzing the neuroeconomic decisions in cocoa producers and the impact of this methodology on the productivity of fair trade organic cocoa producers on the population of Nuevo Bambamarca, province of Tocache, Peru. The main elements of the methodology are the incentive phase of associativity, the alignment phase to macro trends, the prospecting phase of the country to be exported to, the prospecting phase of the type of niche market, the prospecting phase of fair participation, the innovation and design phase of the prototype, the standardization phase of the raw material technical specifications for collection, the strengthening phase the producer’s commitment, the learning phase of the producer in crop management, and the evaluation phase of productivity in the field. This research study is pre-experimental, cross-sectional, explanatory, and descriptive. The experimental group made up of 20 fair trade organic cocoa producers of the Cooperativa Agroindustrial Naranjillo obtained on average a profitability of 143 EUR per campaign higher than the control group made up of 20 producers of conventional cocoa that did not belong to the cooperative who obtained a loss of −642 EUR per campaign, even with the same purchase price of 1.92 EUR per kg for both cases during the 2011 campaign. It is concluded that Hypothesis 1 is met, it shows that the cooperative innovation methodology of prospecting for fair trade organic niche encourages the productivity of producers of the experimental group with respect to the control group.

Abstract 1786: Targeting the immunosuppressive microenvironment of metastatic breast cancer with viroimmunotherapy

Abstract Metastatic breast cancer is the second leading cause of cancer related death among women. Although, conventional therapies such as surgery, adjuvant and neoadjuvant therapies have shown promising outcomes in preclinical and clinical settings, long-term survival rates remain unacceptably low for patients with recurrent disease or disseminated metastases. Breast primary and metastasic niches are characterized by an immunosuppressive microenvironment. Hence, novel therapeutic regimens that modulate this challenging phenotype are desperately needed. Our group has developed and tested in preclinical models and in clinical trials for patients with recurrent glioblastoma the anti-tumor effect of oncolytic adenovirus Delta-24-RGD, also named DNX-2401, resulting with a 20% of long-term survivors, and the awaking of a antitumoral immunity after the administration of the pathogen. This paradigm shift suggests that viroimmunotherapy can be used for the treatment of metastasic cancer. Thus, here we hypothesize that viroimmunotherapy is capable of exerting abscopal effects to eradicate primary breast tumors and their metastatic niches. To test the hypothesis, 4T1 tumor bearing mice were subjected to the local administration of Delta-24-RGD and its armed derivatives, expressing expressing immune co-stimulatory ligands OX40L (Delta-24-RGDOX or DNX-2440) and GITRL (Delta-24-GREAT). We found that, the tumors treated with oncolytic adenoviruses exhibited increase of both CD8+ T cell infiltration and CD8+/CD4+ ratio. Additionally, T-cell activity measured by IFN-γ secretion of splenocytes when in co-culture with breast cancer cells was found to be increased in mice that underwent viroimmunotherapy (P<0.05, ANOVA). In addition, flow cytometry analysis of tumor-infiltrating lymphocites showed a decrease in population of exhausted T cells and MDSCs in tumor microenvironment (P<0.001, ANOVA). Most importantly, animals that underwent viroimmunotherapy showed increase in overall survival (P<0.005, logrank test) with decrease in number of metastatic niches in distant organs as compared to control group. In conclusion, immunological studies indicate that viroimmunotherapy enhances the infiltration and activation of T-cell specific anti-tumor response, stagnating primary tumor growth and metastasis leading ultimately to increase in overall survival. Therefore, we conclude that armed-oncolytic Delta-24-RGD based adenoviruses hold great potential in treatment of primary and metastatic breast cancer. Citation Format: Sagar Shashikant Sohoni, Teresa Nguyen, Dong Ho Shin, Xuejun Fan, Jiang Hong, Sumit Gupta, Ashley Ossimetha, Yanhua Yi, Chandra Bartholomeusz, Marta Alonso, Juan Fueyo, Candelaria Gomez-Manzano. Targeting the immunosuppressive microenvironment of metastatic breast cancer with viroimmunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1786.

Telocytes: An Emerging Component of Stem Cell Niche Microenvironment.

Telocytes (TCs) are newly identified interstitial cells characterized by thin and long cytoplasmic processes, called telopodes, which exhibit a distinctive moniliform shape and, often, a sinuous trajectory. Telopodes typically organize in intricate networks within the stromal space of most organs, where they communicate with neighboring cells by means of specialized cell-to-cell junctions or shedding extracellular vesicles. Hence, TCs are generally regarded as supporting cells that help in the maintenance of local tissue homeostasis, with an ever-increasing number of studies trying to explore their functions both in physiological and pathological conditions. Notably, TCs appear to be part of stem cell (SC) niches in different organs, including the intestine, skeletal muscle, heart, lung, and skin. Indeed, growing evidence points toward a possible implication of TCs in the regulation of the activity of tissue-resident SCs and in shaping the SC niche microenvironment, thus contributing to tissue renewal and repair. Here, we review how the introduction of TCs into the scientific literature has deepened our knowledge of the stromal architecture focusing on the intestine and skeletal muscle, two organs in which the recently unveiled unique relationship between TCs and SCs is currently in the spotlight as potential target for tissue regenerative purposes.

Prostate Cancer Dormancy and Reactivation in Bone Marrow.

Prostate cancer has a variable clinical course, ranging from curable local disease to lethal metastatic spread. Eradicating metastatic cells is a unique challenge that is rarely met with the available therapies. Thus, targeting prostate cancer cells in earlier disease states is a crucial window of opportunity. Interestingly, cancer cells migrate from their primary site during pre-cancerous and malignant phases to seed secondary organs. These cells, known as disseminated cancer cells (DCCs), may remain dormant for months or decades before activating to form metastases. Bone marrow, a dormancy-permissive site, is the major organ for housed DCCs and eventual metastases in prostate cancer. The dynamic interplay between DCCs and the primary tumor microenvironment (TME), as well as that between DCCs and the secondary organ niche, controls the conversion between states of dormancy and activation. Here, we discuss recent discoveries that have improved our understanding of dormancy signaling and the role of the TME in modulating the epigenetic reprogramming of DCCs. We offer potential strategies to target DCCs in prostate cancer.

Postoperative elevation in the plasma CCL2 level is a predictive biomarker of colorectal cancer recurrence.

There is currently no adequate biomarker for predicting colorectal cancer (CRC) recurrence. Chemokine (C-C motif) ligand 2 (CCL2) induces macrophages and fibroblasts to occupy metastatic niches in distant organs. The purpose of this study was to examine CCL2 as a potential predictive biomarker for CRC recurrence. Plasma samples (n = 402) were collected from 80 stage II/III/IV CRC cases and the relationship between CCL2 profiles and recurrence was investigated. The tumor immune response genes associated with CCL2 mRNA expression in a subgroup of 8 stage I/II CRC cases with 12 recurrent sites and The Cancer Genome Atlas database were also analyzed retrospectively. Sixteen stage II/III/IV postoperative recurrent CRC cases experienced a significant increase in plasma CCL2 levels 6months after surgery and continuously increased even after R0-1 resection. The 6-month postoperative CCL2 levels in recurrent cases of ≥ 1year were significantly higher than in non-recurrent cases and recurrent cases of < 1year. The CCL2 level in the primary tumor cases significantly correlated with the cytolytic activity, thus indicating a tumor immune response from the CD163-expressing macrophages. Plasma CCL2 was found to be a predictive biomarker of postoperative CRC recurrence. CCL2 in metastatic sites derives from metastatic niches that surpass the host immune response.