Human Landscape Research Articles

Fires, vegetation, and human—The history of critical transitions during the last 1000 years in Northeastern Mongolia

Fires are natural phenomena that impact human behaviors, vegetation, and landscape functions. However, the long-term history of fire, especially in the permafrost marginal zone of Central Asia (Mongolia), is poorly understood. This paper presents the results of radiocarbon and short-lived radionuclides (210Pb and 137Cs) dating, pollen, geochemical, charcoal, and statistical analyses (Kohonen's artificial neural network) of sediment core obtained from Northern Mongolia (the Khentii Mountains region). Therefore, we present the first high-resolution fire history from Northern Mongolia covering the last 1000 years, based on a multiproxy analysis of peat archive data. The results revealed that most of the fires in the region were likely initiated by natural factors, which were probably related to heatwaves causing prolonged droughts. We have demonstrated the link between enhanced fires and "dzud", a local climatic phenomenon. The number of livestock, which has been increasing for several decades, and the observed climatic changes are superimposed to cause "dzud", a deadly combination of droughts and snowy winter, which affects fire intensity. We observed that the study area has a sensitive ecosystem that reacts quickly to climate change. In terms of changes in the vegetation, the reconstruction reflected climate variations during the last millennium, the degradation of permafrost and occurrence of fires. However, more sites with good chronologies are needed to thoroughly understand the spatial relationships between changing climate, permafrost degradation, and vegetation change, which ultimately affect the nomadic societies in the region of Central and Northern Mongolia.

Functional traits and metacommunity theory reveal that habitat filtering and competition maintain bird diversity in a human shared landscape

Human‐shared landscapes cover much of Earth, yet their conservation value is contested. This controversy may persist because previous studies have examined species diversity, rather than the processes through which such diversity is maintained. For example, a site exhibiting high diversity may not actually bolster populations if the diversity is only maintained through net immigration. Recent research has begun to isolate the processes that maintain metacommunities and develop functional trait methods to identify these processes. However, the processes underlying bird communities remain obscure. Here, we leverage metacommunity theory, functional trait partitioning and a Bayesian multispecies abundance model to assess whether a shared landscape – woody perennial polyculture farms – bolsters bird diversity. Such farms grow multiple species of food‐producing woody perennials together with vegetative groundcover. We surveyed birds and their in situ functional traits across the US Midwest in traditional agriculture, woody perennial polyculture, prairie and woods. We found that woody perennial polycultures exhibited the highest bird diversity and were the most preferred by many species (including threatened ones). Moreover, our functional trait analysis suggests that this diversity is maintained through habitat filtering and competition, rather than merely immigration. Thus, shared landscapes can likely conserve birds by providing a distinct habitat. These results suggest that woody perennial polyculture farms offer substantial potential to support bird populations in the US Midwest. Our study demonstrates the utility of in situ functional trait partitioning within a Bayesian framework to unmask ecological processes and help assess the conservation value of landscapes.

Global assessment of storm disaster-prone areas.

Advances in climate change research contribute to improved forecasts of hydrological extremes with potentially severe impacts on human societies and natural landscapes. Rainfall erosivity density (RED), i.e. rainfall erosivity (MJ mm hm-2 h-1 yr-1) per rainfall unit (mm), is a measure of rainstorm aggressiveness and a proxy indicator of damaging hydrological events. Here, using downscaled RED data from 3,625 raingauges worldwide and log-normal ordinary kriging with probability mapping, we identify damaging hydrological hazard-prone areas that exceed warning and alert thresholds (1.5 and 3.0 MJ hm-2 h-1, respectively). Applying exceedance probabilities in a geographical information system shows that, under current climate conditions, hazard-prone areas exceeding a 50% probability cover ~31% and ~19% of the world's land at warning and alert states, respectively. RED is identified as a key driver behind the spatial growth of environmental disruption worldwide (with tropical Latin America, South Africa, India and the Indian Archipelago most affected).

Conceptualising and Implementing an Agent-Based Model of an Irrigation System

The literature on irrigated agriculture is primarily concerned with irrigation techniques, irrigation water-use efficiency, and crop yields. How human and non-human agents co-shape(d) irrigation landscapes through their activities and how these actions impact long-term developments are less well studied. In this study, we aim to (1) explore interactions between human and non-human agents in an irrigation system; (2) model the realistic operation of an irrigation system in an agent-based model environment, and; (3) study how short-term irrigation management actions create long-term irrigation system patterns. An agent-based model (ABM) was used to build our Irrigation-Related Agent-Based Model (IRABM). We implemented various scenarios, combining different irrigation control methods (time versus water demand), different river discharges, varied gate capacities, and several water allocation strategies. These scenarios result in different yields, which we analyse on the levels of individual farmer, canal, and system. Demand control gives better yields under conditions of sufficient water availability, whereas time control copes better with water deficiency. As expected, barley (Hordeum vulgare, Poaceae) yields generally increase when irrigation time and/or river discharge increase. The effect of gate capacity is visible with yields not changing linearly with changing gate capacities, but showing threshold behaviour. With the findings and analysis, we conclude that IRABM provides a new perspective on modelling the human-water system, as non-human model agents can create the dynamics that realistic irrigation systems show as well. Moreover, this type of modelling approach has a large potential to be theoretically and empirically used to explore the interactions between irrigation-related agents and understand how these interactions create water and yields patterns. Furthermore, the developed user-interface model allows non-technical stakeholders to participate and play a role in modelling work.

Stream water quality optimized prediction based on human activity intensity and landscape metrics with regional heterogeneity in Taihu Basin, China.

The driving effects of landscape metrics on water quality have been acknowledged widely, however, the guiding significance of human activity intensity and landscape metrics based on reference conditions for water environment management remains to be explored. Thus, we used the self-organized map, long- and short-term memory (LSTM) algorithm, and geographic detectors to simulate the response of human activity intensity and landscape metrics to water quality in Taihu Lake Basin, China. Fitting results of LSTM displayed that the accuracy was acceptable, and scenario 2 (regional heterogeneity) was more efficient than scenario 1 (regional consistent) in the improvement of water quality. In the driving analysis for the reference conditions, clusters I and II (urban agglomeration areas) were mainly affected by the amount of production wastewater per unit of developed land and the amount of livelihood wastewater per unit of developed land, respectively. Their optimal values were 0.09 × 103 t/km2 (reduction of 35.71%) and 0.2 × 103 t/km2 (reduction of 4.76%). Cluster III (agricultural production areas) was mainly affected by interference intensity, and the optimal value was 2.17 (increased 38.22%), and cluster IV (ecological forest areas) was mainly affected by the fragmentation of cropland, and the optimal value was 1.14 (reduction of 1.72%). The research provides a reference for the prediction of water quality response and presents an ecological and economic sustainability way for watershed governance.

MiRSCAPE - inferring miRNA expression from scRNA-seq data

SummaryOur understanding of miRNA activity at cellular resolution is thwarted by the inability of standard scRNA-seq protocols to capture miRNAs. We introduce a novel tool, miRSCAPE, to infer miRNA expression in a sample from its RNA-seq profile. We establish miRSCAPE’s accuracy in 10 tumor and normal cohorts demonstrating its superiority over alternatives. miRSCAPE accurately infers cell type-specific miRNA activities (predicted versus observed fold-difference correlation ∼0.81) in two independent scRNA-seq datasets. We apply miRSCAPE to infer miRNA activities in scRNA clusters in pancreatic and lung adenocarcinomas, as well as in 56 cell types in the human cell landscape (HCL). In pancreatic and breast cancer scRNA-seq data, miRSCAPE recapitulates miRNAs associated with stemness and epithelial-mesenchymal transition (EMT) cell states, respectively. Overall, miRSCAPE recapitulates and refines miRNA biology at cellular resolution. miRSCAPE is freely available and is easily applicable to scRNA-seq data to infer miRNA activities at cellular resolution.

Improving Soundscape Comfort in Urban Green Spaces Based on Aural-Visual Interaction Attributes of Landscape Experience

The importance of multi-sensory perception in constructing human landscape experiences has been increasingly emphasized in contemporary urban life. The aim of this study is to explore aural-visual interaction attributes that may influence people’s perceived overall soundscape comfort in urban green spaces (UGSs). To achieve this, a total of 12 perceptive indicators were identified from the existing literature to evaluate people’s perceived visual and acoustic attributes and types of sound sources, and their relations to the perceived soundscape comfort. 268 responses were obtained in a questionnaire-based survey conducted in five UGSs in Chengdu Outer Ring Ecological Zone. This was done whilst a typical objective acoustic indicator, sound level, was used as a mediator for potential changes on these relations within different sound level ranges. Results suggested that a low level of environmental sound does not correspond to higher ratings on the overall soundscape comfort. It was also found that the environmental sound level of 77 dBA was a turning point in the relation between people’s soundscape comfort and its influential indicators in UGSs. A set of six models was then provided to describe the overall soundscape comfort and its contributing indicators in aural-visual interactions, respectively, in sound level ranges below and above 77dBA.

Can Our [New] Cities Survive?

The developmental growth of home-improving devices and equipment has ceaselessly progressed from the Industrial Revolution until the present day. From heating systems to lighting equipment and air conditioning, we have now reached the Smart house age. However, in order to be efficient, such a kind of home demands a new city: A Smart City, with devices, networks, and infrastructures that would be fundamental requisites for its functioning. That is why the ancient cities, on the way to becoming an inconvenience for the development of the brand-new ones, are going to find their place in a desert, in a "tabula rasa" devoid of relics, ruins, and debris of their history. This contribution investigates the challenges that architects must put forth in trying to overcome such a condition of exclusion from the process of building a new human landscape.

Lessons from a lakebed: unpicking hydrological change and early human landscape use in the Makgadikgadi basin, Botswana

The intersection of archaeological material with the landscape is investigated using OSL dating of landforms associated with Middle Stone Age (MSA) archaeology in the Makgadikgadi basin, Botswana. In this study, MSA archaeological sites on the Makgadikgadi pan floor date to two dry periods in the basin during the late Quaternary. Site formation at one site occurred during dry, or seasonally dry conditions that followed a period of high lake levels between 128 ± 18 ka and 81 ± 6 ka. The site was buried by sediments from a subsequent period of high lake levels dating to between 72 ± 5 ka and 57 ± 8 ka. At other investigated sites, the archaeological material was most likely deposited during a second dry period sometime after this. Overlying dunes are much younger (late Holocene) than the late Pleistocene lakebed sediments associated with the archaeological sites. Rapid burial of the archaeological sites by clayey sands has resulted in limited disturbance and weathering of archaeological material which appears to have only been exposed very recently, perhaps in the last 350 years when conditions have been particularly dry and susceptible to deflation. The spatial patterning of both sediment accumulation and deflation strongly influences archaeological visibility both within and around the Makgadikgadi basin.

Frontier, Identity Constructions and Environment. Water as an Essential Condition for Viewing the Muslim Other in the Journey to the Iberian Peninsula by the Physician Hieronymus Münzer (1494-1495)

Between 1494 and 1495, the German physician Hieronymus Münzer travelled to the Iberian Peninsula, which resulted in an extensive written testimony traditionally known as Itinerarium. The main focus of this northern traveller's observations is not the human element, as several authors have already pointed out. In fact, he focuses his attention especially on the economic element (products, goods, trade, etc.) and, by association, the territories and places where this element takes place. However, he also unquestionably develops evaluative perspectives of the Iberian human landscape, in its most diverse expressions. We sought to reflect precisely upon one of the components of the human sphere the northern traveller contacted – the Muslims –, with special consideration for the resulting identity constructions and alterity exercises, which, in our perspective, are often closely associated with the central issue of water and, consequently, with the territories/places visited and the intrinsic frontiers. We looked for the answer to, what we consider, a paramount and truly original question: to what extent does water assume a "centrality" in this northern European doctor's view of the Other, specifically the Muslim, in the context of direct observation and first-hand experience.

Paisagens de Macau (sécs. XVIII-XIX). “Vue de Macao en Chine” versus” On the Green”

O Museu do Centro Científico e Cultural de Macau (CCCM) conserva no seu acervo uma gravura e um desenho com vistas da cidade de Macau, dos finais do séc. XVIII e da primeira metade do séc. XIX. A primeira, “Vue de Macao en Chine”, data de 1787 e é da autoria de Gaspard Duché de Vancy e o segundo, “On the Green”, um pouco mais tardio, é do ano de 1838 e foi desenhado por Warner Varnham.
 Estes dois exemplares oferecem-nos perspectivas complementares e extremamente interessantes da cidade de Macau. Nos mesmos é possível reconhecer paisagens físicas e humanas e reconstituir ambientes.
 Estas imagens serão analisadas em paralelo, nas suas semelhanças e diferenças e, no âmbito deste estudo, serão cruzadas com memórias escritas coevas, de forma a atingir-se outros níveis de compreensão e de leitura da realidade da época, para além da dimensão estritamente visual que as mesmas encerram.

An Evaluation of National Park System Pilot Area Using the AHP-Delphi Approach: A Case Study of the Qianjiangyuan National Park System Pilot Area, China

With the national park as an important measure of ecological protection, China has started 10 national park system pilot areas. However, the research on the comprehensive evaluation of national park construction and development is insufficient. The main purpose of this study was to establish a comprehensive evaluation index system for the pilot area of the national park system. The method of the Analytic Hierarchy Process combined with the Delphi method by ten relevant experts was used. The comprehensive evaluation index system for the national park system pilot areas was composed of the objective level and the criteria level which includes three items: natural resource conditions; research, education and recreation functions; and protection and management conditions. The indicator level involved seven items and the factor level included 31 items. Furthermore, the weight of each item in these levels was obtained through the Delphi method by the judgement of selected experts. The Qianjiangyuan National Park System Pilot Area (QNPSPA) was selected as the study case for empirical research. The score of the comprehensive evaluation of the QNPSPA was 90.801, which belongs to Grade I in the five catalogues, indicating its comprehensive construction level was very high and its protection and management measures were efficient. However, significant deficiencies also existed in the area suitability, recreation facilities and production, natural resource property rights, human landscape value and ecosystem integrity. To address these problems, five suggestions were proposed. For example, strengthening cross-administrative cooperation and communication, improving the construction of recreational facilities, etc. The evaluation framework proposed in this study could play a positive role in the construction evaluation of the pilot areas of national parks in China and is conducive to promoting the evaluation research of national parks in China and promoting the development of conservation and construction.

LB891 MANTIS: An integrated digital process for 3-D deconstruction of human skin immune landscape

The human skin is a tightly-organized ecosystem composed of a dense network of thick structural appendices surrounding naturally-resident and recruited immune cells. Routine clinical assays, such as conventional immunohistochemistry, fail to resolve the regional heterogeneity and immune topology of inflammatory skin conditions, which can lead to false interpretation. Here we introduce MANTIS (Multiplexed Annotated Tissue Imaging System), a flexible analytical system specifically designed for spatially-resolved immune-phenotyping of the skin in thick experimental samples or large clinical cohorts. Combining multiplexed 3-D imaging, machine learning and unsupervised bioinformatics, MANTIS automatically projects a representative digital immune landscape, while enabling interactive gating of anatomical regions and concomitant single-cell data quantification of biomarkers. We leverage these properties to analyze skin biopsies from healthy and pathological conditions.

Increased MPO in Colorectal Cancer Is Associated With High Peripheral Neutrophil Counts and a Poor Prognosis: A TCGA With Propensity Score-Matched Analysis.

BackgroundMyeloperoxidase (MPO) has been demonstrated to be a local mediator of inflammation in tissue damage in various inflammatory diseases. Given its controversial effect on colorectal cancer (CRC), there has been growing interest in investigating the role of this enzyme in CRC. The mechanism underlying MPO activity and CRC progression requires further clarification.MethodsThe expression and function of MPO in CRC were evaluated using TCGA analysis. TCGA, TIMER, and Human Cell Landscape analyses were used to analyze the correlation between MPO expression and neutrophil infiltration in CRC. Spearman’s bivariate correlation analysis was used to verify the correlation between MPO levels in CRC and the peripheral neutrophil count. In the clinical analysis, 8,121 patients who underwent elective surgery for CRC were enrolled in this retrospective cohort study from January 2008 to December 2014. Propensity score matching was used to address the differences in baseline characteristics. The Kaplan–Meier method and Cox regression analysis were used to identify independent prognostic factors in patients with CRC.ResultsMPO was upregulated in CRC tissues, which is related to malignant progression and worse survival in CRC patients from TCGA analysis. MPO was significantly correlated with the infiltration level of neutrophils in CRC in TCGA, TIMER, and Human Cell Landscape analyses. MPO was positively correlated with the peripheral neutrophil count. Data of the 8,121 patients who underwent CRC surgery were available for analysis. After propensity score matching, 3,358 patients were included in each group. Kaplan–Meier survival curves showed that high preoperative neutrophil levels were associated with decreased overall survival (OS; P < 0.001) and disease-free survival (DFS; P = 0.015). The preoperative neutrophil count was an independent risk factor for OS (hazard ratio [HR], 1.157; 95% confidence interval [CI], 1.055–1.268; P = 0.002) and DFS (HR, 1.118; 95% CI, 1.009–1.238; P = 0.033).ConclusionsOur research indicates that increased MPO levels in CRC are significantly correlated with high preoperative neutrophil counts, and both serve as prognostic indicators for worse survival in CRC patients. Our study suggests that neutrophils may be key players in the mechanism linking MPO levels with poor CRC outcomes.

Environmental Aesthetics Revived in Taiwan : Implications of Socially-engaged Art Practice and Local Art Festival

&lt;p&gt;自1990年代後期以來，臺灣當代藝術發展出社會參與式藝術實踐的趨勢，亦即走出美術館展覽的藩籬並企求與公眾面對面、與社群連結的藝術創作。此一歷程發展適逢後解嚴時代，在地文化認同與本土意識抬頭，反映在文化政策上的則是1990年代的社區總體營造運動乃至於近年來倡議的地方創生。此後，各地的藝術祭更是持續不斷地帶來參與者對地方人文與環境的新感受，發展出在獨特的臺灣文化脈絡與社會變遷的背景下所帶動的「環境美學」復興&amp;mdash;&amp;mdash;對自然與人文環境的重新發現，以及對地方文化歷史脈絡的重思與再建構。對環境與地方的自然和人文關懷是目前亞洲地區正歷時與共的境況，本文以臺灣的社會參與式藝術和地方藝術祭為主要探討對象，自其所帶來的環境美學復興，延伸思考社會參與式藝術暨地方藝術祭的亞洲觀點所帶來的啟示，並以更全觀的視角來思辨藝術的社會實踐，啟發藝術工作者，面對此一全球共同的環境議題。&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;&lt;p&gt;Since the late 1990s, Taiwanese contemporary art has developed a trend of socially-engaged art practice that goes beyond the usual framework of museum exhibition and with the aim of reaching public audiences. Moreover, such progress involves a degree of community engagement. The post-Martial law era saw the emergence of issues of local cultural identity and the rise of ideologies of the vernacular. Equally, socially-engaged art practice in Taiwan addressed throughout the 1990s issues of cultural policies for community reconstruction and ideas of &amp;ldquo;creative placemaking&amp;rdquo;. The result of such trend has also brought the prevalence of local art festivals. Such a socially art practice and local art festival has since developed into a genuine environmental aesthetics that has led to the rediscovery of human landscape, the natural environment, and to the reconstruction of local culture and history. This latter specificity, though, differs from its Western counterpart model of social art practice.This paper will explore the socially-engaged art and local art festival in Taiwan, their process of development, content and approach through surveys and fieldwork. Their relations to each other, differences, similarities, and sustainability will be also discussed in this research. However, the impacts that they triggered for the revival of environmental aesthetics, has significances to what are related to ecological and environmental issues in the whole world. Attending for local environment, people, history and culture is currently experienced in the Asia is also a common issue. This research takes socially-engaged art practice and local art festivals as a subject, as well as addressing their implications on revival of environmental aesthetics in Taiwan. Moreover, this research not only intends to expound socially-engaged art practice and local art festival from the local perspectives of Taiwan; it also seeks to enrich how we understand such practice in a broader Asian and even global contexts. &lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

Decline or Rejuvenation? Efficiency Development of China’s National Scenic Areas

The decline is one of the essential issues for developing tourism destinations. The rapid adoption of appropriate policies will enable them to reverse the decline and enter the rejuvenation stage in time. This study advocated establishing an operational evaluation model of tourism efficiency with DEA and the super-SBM model to estimate when China’s mass tourism destinations are in decline and rejuvenation based on the tourism area life cycle (TALC) theory regarding China’s national scenic areas (NSAs) samples. The results show that the development of China’s mass tourism destinations can be divided into three phases, in which there is a clear process of persistent decline and rejuvenation. Different types of NSAs vary in terms of efficiency level and change trends. Human landscape, caves, and wetland and lakes all have distinct phases of persistent decline, but humanistic landscapes show a significant rejuvenation trend. These findings provide an innovative re-interpretation of the TALC model.

Network-Based Methods for Approaching Human Pathologies from a Phenotypic Point of View.

Network and systemic approaches to studying human pathologies are helping us to gain insight into the molecular mechanisms of and potential therapeutic interventions for human diseases, especially for complex diseases where large numbers of genes are involved. The complex human pathological landscape is traditionally partitioned into discrete “diseases”; however, that partition is sometimes problematic, as diseases are highly heterogeneous and can differ greatly from one patient to another. Moreover, for many pathological states, the set of symptoms (phenotypes) manifested by the patient is not enough to diagnose a particular disease. On the contrary, phenotypes, by definition, are directly observable and can be closer to the molecular basis of the pathology. These clinical phenotypes are also important for personalised medicine, as they can help stratify patients and design personalised interventions. For these reasons, network and systemic approaches to pathologies are gradually incorporating phenotypic information. This review covers the current landscape of phenotype-centred network approaches to study different aspects of human diseases.

Audio-Visual Preferences for the Exercise-Oriented Population in Urban Forest Parks in China

The purpose of this study is to explore the audio-visual preferences of exercisers in urban forest parks in China and to make practical suggestions for park landscape design. Taking Beigushan Forest Park in Lianyungang City, Jiangsu Province as a case, based on field research and questionnaire survey, this study analyzed the audio-visual preference characteristics of exercisers in the park, revealed the correlation between audio-visual preference and exercisers’ behaviors and individual characteristics, and explored the influence of audio-visual preferences on exercise feelings by establishing a structural equation model. It was found that (1) the forest and its avenue landscape and birdsong are most preferred by exercisers; (2) the audio-visual preferences of people with different exercise forms differ, for example, people who slowly walk, run, and briskly walk have stronger preferences for natural soundscape and visual landscape, while people who use fitness equipment have stronger inclusiveness for human activity sound and prefer public facility-based landscapes. In addition, some individual characteristics such as exercise intensity and exercise frequency significantly affect exercisers’ audio-visual preferences; (3) visual landscape preferences have a greater direct impact on exercise feelings, with natural waterscape having the greatest direct impact, but overall soundscape preferences do not have a high degree of direct impact on exercise feelings, with natural sound still having a strong positive impact. These findings provide a more quantitative basis for the landscape design of urban forest parks from the perspective of exercise behavior.

Abstract 4082: Expression of chimeric antigen receptor therapy targets in subpopulations detected by single-cell sequencing of normal cells may contribute to off-tumor toxicity

Abstract Chimeric antigen receptor (CAR)-engineered cell therapy, which leverages genetically modified immune cells to generate a tailored immune response, has revolutionized cancer treatment (Dougan et al., 2021; Hong et al., 2020). The number, type and indications of clinical trials for CAR-engineered cell therapies have increased rapidly in recent years (MacKay et al., 2020). However, serious and potentially life-threaten toxicities, such as on-target, off-tumor effects, remain a major limitation of CAR-engineered cell therapies (Dougan et al., 2021; MacKay et al., 2020). To better understand the effects of CAR-directed immunotherapy, a systematic single-cell-level dissection of the expression of divergent CAR targets in various cell types across different normal tissues is urgently required. We analyzed the expression of 591 CAR targets, including 71 that were employed in clinical trials up to January 2021 and 520 that were predicted to have favorable safety profiles (MacKay et al., 2020), in two independent single-cell cohorts, including 342,755 adult cell scRNA-seq data from human cell landscape (HCL) based on Microwell-seq (Han et al., 2020), and 84,363 adult cell scRNA-seq data from adult human cell atlas (AHCA) based on 10× Genomics (He et al., 2020). We used a stringent cutoff by defining a CAR target as a potentially risky gene (PRG) if it was measurable in more than 100 non-immune cells and more than 2% of the total cells in at least three normal tissues. We identified 92 and 88 PRGs from HCL and AHCA by employing this criterion, with 57 PRGs shared in both HCL and AHCA datasets (hypergeometric test p = 7.17×10-29), suggesting the robustness of our analysis. To aid the research community in the design of CAR targets, we developed a user-friendly data portal, CAR target gene toxicity at single-cell level (CARTSC) (https://hanlab.tamhsc.edu/CARTSC/), to allow for browsing and searching the single target and logical ‘and’ design switch expressions at the single-cell level. Citation Format: Ying Jing, Yuan Liu, Qiang Li, Leng Han. Expression of chimeric antigen receptor therapy targets in subpopulations detected by single-cell sequencing of normal cells may contribute to off-tumor toxicity [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 4082.

Abstract 5148: Immune landscapes and interactions in human fallopian tubes and their implications for early high-grade serous ovarian cancers

Abstract The five-year survival rate of ovarian cancer (OC) dramatically rises from below 40% to 90% with patients who are diagnosed early (stage I), when the disease restricts to the ovary. Thus, the ultimate goals of our research are to learn how to detect ovarian cancer at its earliest stages of development and thereby improve patient survival and to learn how the immune microenvironment contributes to the development of OC. Achieving these goals requires us to better characterize the earliest steps in ovarian carcinogenesis. The human fallopian tube harbors the cell-of-origin for most high-grade serous 'ovarian' cancers (HGSOCs), but its cellular composition, particularly the immune component, is poorly characterized. Emerging evidence from several research groups using molecular sequencing technologies of fallopian tube epithelium strongly support this hypothesis. We recently described our use of single-cell transcriptome technology (scRNA-Seq) to profile the heterogeneity of non-malignant FT and define a novel transcriptional gene regulatory network of epithelial differentiation and tumorigenesis in the human FT. Here we present an in-depth characterization of the immune cell atlas for human fallopian tubes, which has not been reported. Our unpublished analyses of our FT dataset and the publicly available HGSOC scRNA-Seq dataset demonstrate a significant difference in the immune cell landscape. There are limited macrophages and a high abundance of monocytes in non-malignant FT and adjacent normal ovaries compared to those in HGSOC tumors. This finding leads us to hypothesize that the macrophage-to-monocyte ratio and their interactions with other immune cell types in human fallopian tubes create a permissive microenvironment allowing for the development of HGSOC and can provide a biomarker for early cancer detection. To test if those myeloid cells could be a marker for early HGSOC, we performed scRNA-seq on FT from women carrying mutant alleles of BRCA1 or BRCA2 who are at high risk of HGSOC. Intriguingly, the ratio of monocytes to macrophages in the FTs from half of these high-risk individuals is more like that found in HGSOC than in normal FT. Furthermore, computational analyses on myeloid cell types and their interactions with different epithelial cells, stromal fibroblast cells, and T and NK cells revealed the extended contribution of the non-epithelial microenvironment in FT, potentially driving early HGSOC development and progression. This cellular and molecular compendium of the human fallopian tube immune landscapes in cancer-free and cancer-high-risk women is expected to advance our understanding of the earliest stages of fallopian epithelial neoplasia. Citation Format: Josh Brand, Marcela Harro, Forough Abbasi, Xianzhi Lin, Matthew Siedhoff, Li Andrew, Bobbie J. Rimel, Fabiola Medeiros, Kate Lawrenson, Huy Q. Dinh. Immune landscapes and interactions in human fallopian tubes and their implications for early high-grade serous ovarian cancers [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 5148.