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Objectives. To assess wildfire risks to California inpatient health care facilities in 2022. Methods. Locations of inpatient facilities and associated inpatient bed capacities were mapped in relation to California Department of Forestry and Fire Protection fire threat zones (FTZs), which combine expected fire frequency with potential fire behavior. We computed the distances of each facility to the nearest high, very high, and extreme FTZs. Results. Half (107 290 beds) of California’s total inpatient capacity is within 0.87 miles of a high FTZ and 95% (203 665 beds) is within 3.7 miles of a high FTZ. Half of the total inpatient capacity is within 3.3 miles of a very high FTZ and 15.5 miles of an extreme FTZ. Conclusions. Wildfires threaten a large number of inpatient health care facilities in California. In many counties, all health care facilities may be at risk. Public Health Implications. Wildfires in California are rapid-onset disasters with short preimpact phases. Policies should address facility-level preparedness including smoke mitigation, sheltering measures, evacuation procedures, and resource allocation. Regional evacuation needs, including access to emergency medical services and patient transportation, must also be considered. (Am J Public Health. 2023;113(5):555–558. https://doi.org/10.2105/AJPH.2023.307236 )

Scientists are frequently called upon to “democratize” science, by bringing the public into scientific research. One appealing point for public involvement concerns the nonepistemic values involved in science. Suppose, though, a scientist invites the public to participate in making such value-laden determinations but finds that the public holds values the scientist considers morally unacceptable. Does the argument for democratizing science commit the scientist to accepting the public’s objectionable values, or may she veto them? I argue that there are a limited set of cases in which scientists can, consistently with a commitment to democratized science, set aside the public’s judgments.

Innate lymphoid cells (ILCs) are tissue-resident effectors poised to activate rapidly in response to local signals such as cytokines. To preserve homeostasis, ILCs must employ multiple pathways, including tonic suppressive mechanisms, to regulate their primed state and prevent inappropriate activation and immunopathology. Such mechanisms remain incompletely characterized. Here we show that cytokine-inducible SH2-containing protein (CISH), a suppressor of cytokine signaling (SOCS) family member, is highly and constitutively expressed in type 2 innate lymphoid cells (ILC2s). Mice that lack CISH either globally or conditionally in ILC2s show increased ILC2 expansion and activation, in association with reduced expression of genes inhibiting cell-cycle progression. Augmented proliferation and activation of CISH-deficient ILC2s increases basal and inflammation-induced numbers of intestinal tuft cells and accelerates clearance of the model helminth, Nippostrongylus brasiliensis, but compromises innate control of Salmonella typhimurium. Thus, CISH constrains ILC2 activity both tonically and after perturbation, and contributes to the regulation of immunity in mucosal tissue.

There is a growing consensus among philosophers of science that core parts of the scientific process involve non-epistemic values. This undermines the traditional foundation for public trust in sci...

Philosophers of science now broadly agree that doing good science involves making non-epistemic value judgments. I call attention to two very different normative standards which can be used to evaluate such judgments: standards grounded in ethics and standards grounded in political philosophy. Though this distinction has not previously been highlighted, I show that the values in science literature contain arguments of each type. I conclude by explaining why this distinction is important. Seeking to determine whether some value-laden determination meets substantive ethical standards is a very different endeavor from seeking to determine if it is politically legitimate.

Scientists have the ability to influence policy in important ways through how they present their results. Surprisingly, existing codes of scientific ethics have little to say about such choices. I propose that we can arrive at a set of ethical guidelines to govern scientists' presentation of information to policymakers by looking to bioethics: roughly, just as a clinician should aim to promote informed decision-making by patients, a scientist should aim to promote informed decision-making by policymakers. Though this may sound like a natural proposal, I show it offers guidance that conflicts with standard scientific practices. I conclude by considering one cost of the proposal: that it would prevent scientists from acting as advocates in a way that is currently common in certain fields. I accept that the proposal would restrict scientists' political advocacy rights, but argue that the benefits of adopting it-promoting democratic governance-justify the restriction.

During certain public health emergencies, points of dispensing (PODs) may be used to rapidly distribute medical countermeasures such as antibiotics to the general public to prevent disease. Jurisdictions across the country have identified sites for PODs in preparation for such an emergency; in New York City (NYC), the sites are identified based largely on population density. Vulnerable populations, defined for this analysis as persons with income below the federal poverty level, persons with less than a high school diploma, foreign-born persons, persons of color, persons aged ≥65 years, physically disabled persons, and unemployed persons, often experience a wide range of health inequities. In NYC, these populations are often concentrated in certain geographic areas and rely heavily on public transportation. Because public transportation will almost certainly be affected during large-scale public health emergencies that would require the rapid mass dispensing of medical countermeasures, we evaluated walking distances to PODs. We used an ordinary least squares (OLS) model and a geographically weighted regression (GWR) model to determine if certain characteristics that increase health inequities in the population are associated with longer distances to the nearest POD relative to the general NYC population. Our OLS model identified shorter walking distances to PODs in neighborhoods with a higher percentage of persons with income below the federal poverty level, higher percentage of foreign-born persons, or higher percentage of persons of color, and identified longer walking distances to PODs in neighborhoods with a higher percentage of persons with less than a high school diploma. Our GWR model confirmed the findings from the OLS model and further illustrated these patterns by certain neighborhoods. Our analysis shows that currently identified locations for PODs in NYC are generally serving vulnerable populations equitably—particularly those defined by race or income status—at least in terms of walking distance.

Type 2 T helper (TH2) cells are protective against parasitic worm infections but also aggravate allergic inflammation. Although the role of dendritic cells (DCs) in TH2 cell differentiation is well...

Disasters, such as cyclones, create conditions that increase the risk of infectious disease outbreaks. Epidemic forecasts can be valuable for targeting highest risk populations before an outbreak. The two main barriers to routine use of real-time forecasts include scientific and operational challenges. First, accuracy may be limited by availability of data and the uncertainty associated with the inherently stochastic processes that determine when and where outbreaks happen and spread. Second, even if data are available, the appropriate channels of communication may prevent their use for decision making.In April 2019, only six weeks after Cyclone Idai devastated Mozambique’s central region and sparked a cholera outbreak, Cyclone Kenneth severely damaged northern areas of the country. By June 10, a total of 267 cases of cholera were confirmed, sparking a vaccination campaign. Prior to Kenneth’s landfall, a team of academic researchers, humanitarian responders, and health agencies developed a simple model to forecast areas at highest risk of a cholera outbreak. The model created risk indices for each district using combinations of four metrics: (1) flooding data; (2) previous annual cholera incidence; (3) sensitivity of previous outbreaks to the El Niño-Southern Oscillation cycle; and (4) a diffusion (gravity) model to simulate movement of infected travelers. As information on cases became available, the risk model was continuously updated. A web-based tool was produced, which identified highest risk populations prior to the cyclone and the districts at-risk following the start of the outbreak.The model prior to Kenneth’s arrival using the metrics of previous incidence, projected flood, and El Niño sensitivity accurately predicted areas at highest risk for cholera. Despite this success, not all data were available at the scale at which the vaccination campaign took place, limiting the model’s utility, and the extent to which the forecasts were used remains unclear. Here, the science behind these forecasts and the organizational structure of this collaborative effort are discussed. The barriers to the routine use of forecasts in crisis settings are highlighted, as well as the potential for flexible teams to rapidly produce actionable insights for decision making using simple modeling tools, both before and during an outbreak.

Author(s): Fassett, Marlys S; Braz, Joao M; Castellanos, Carlos A; Schroeder, Andrew W; Sadeghi, Mahsa; Mar, Darryl J; Zhou, Connie J; Shin, Jeoung-Sook; Basbaum, Allan I; Ansel, K Mark | Abstract: ABSTRACTDespite a robust literature associating IL-31 with pruritic inflammatory skin diseases, its influence on cutaneous inflammation and on the interplay between inflammatory and neurosensory pathways remain unmapped. Here, we examined the effects of IL-31 and its receptor IL31RA on both inflammation and pruritus in mouse models of dermatitis, including chronic topical house dust mite (HDM) exposure. Unexpectedly, Il31 deficiency increased cutaneous adaptive type 2 cytokine-producing cells and serum IgE. In addition, M2-like macrophages capable of fueling feedforward pro-inflammatory loops were selectively enriched in Il31ra-deficient skin. Thus, IL-31 is not strictly a pro-inflammatory cytokine, but rather an immunoregulatory factor that limits the magnitude of allergic skin inflammation. In contrast, Il31-deficient mice displayed a deficit in HDM-induced scratching. Itch reduction occurred despite intact – and in some cases increased – responsiveness of sensory neurons to other pruritogens released during HDM challenge, highlighting the non-redundant contribution of IL-31-receptive sensory afferents to pruritus in environmental allergen-induced dermatitis. When present, therefore, IL-31 uncouples circuits driven by sensory neurons and immune cells that converge in inflamed skin.

T cell anergy is an important peripheral tolerance mechanism to prevent autoimmunity. Nguyen et al. find that T cell anergy develops in the periphery, not in the thymus, and depends upon Cbl-b but not Grail or PD-1., T cell anergy is an important peripheral tolerance mechanism. We studied how T cell anergy is established using an anergy model in which the Zap70 hypermorphic mutant W131A is coexpressed with the OTII TCR transgene (W131AOTII). Anergy was established in the periphery, not in the thymus. Contrary to enriched tolerance gene signatures and impaired TCR signaling in mature peripheral CD4 T cells, CD4SP thymocytes exhibited normal TCR signaling in W131AOTII mice. Importantly, the maintenance of T cell anergy in W131AOTII mice required antigen presentation via MHC-II. We investigated the functional importance of the inhibitory receptor PD-1 and the E3 ubiquitin ligases Cbl-b and Grail in this model. Deletion of each did not affect expression of phenotypic markers of anergic T cells or T reg numbers. However, deletion of Cbl-b, but not Grail or PD-1, in W131AOTII mice restored T cell responsiveness and signaling. Thus, Cbl-b plays an essential role in the establishment and/or maintenance of unresponsiveness in T cell anergy., Graphical Abstract

The IHME Covid-19 prediction model has been one of the most influential Covid models in the United States. Early on, it received heavy criticism for understating the extent of the epidemic. I argue that this criticism was based on a misunderstanding of the model. The model was best interpreted not as attempting to forecast the actual course of the epidemic. Rather, it was attempting to make a conditional projection: telling us how the epidemic would unfold, given certain assumptions. This misunderstanding of the IHME’s model prevented the public from seeing how dire the model’s projections actually were.

Chronic kidney disease (CKD) and acute kidney injury (AKI) are common, heterogeneous, and morbid diseases. Mechanistic characterization of CKD and AKI in patients may facilitate a precision medicine approach to prevention, diagnosis, and treatment. The Kidney Precision Medicine Project aims to ethically and safely obtain kidney biopsies from participants with CKD or AKI, create a reference kidney atlas, and characterize disease subgroups to stratify patients based on molecular features of disease, clinical characteristics, and associated outcomes. An additional aim is to identify critical cells, pathways, and targets for novel therapies and preventive strategies. This project is a multicenter prospective cohort study of adults with CKD or AKI who undergo a protocol kidney biopsy for research purposes. This investigation focuses on kidney diseases that are most prevalent and therefore substantially burden the public health, including CKD attributed to diabetes or hypertension and AKI attributed to ischemic and toxic injuries. Reference kidney tissues (for example, living kidney donor biopsies) will also be evaluated. Traditional and digital pathology will be combined with transcriptomic, proteomic, and metabolomics analysis of the kidney tissue as well as deep clinical phenotyping for supervised and unsupervised subgroup analysis and systems biology analysis. Participants will be followed prospectively for ten years to ascertain clinical outcomes. Cell types, locations, and functions will be characterized in health and disease in an open, searchable, online kidney tissue atlas. All data from the Kidney Precision Medicine Project will be made readily available for broad use by scientists, clinicians, and patients.

Alveolar formation increases the surface area for gas exchange. A molecular understanding of alveologenesis remains incomplete. Here, we show that the autonomic nerve and alveolar myofibroblast form a functional unit in mice. Myofibroblasts secrete neurotrophins to promote neurite extension/survival, whereas neurotransmitters released from autonomic terminals are necessary for myofibroblast proliferation and migration, a key step in alveologenesis. This establishes a functional link between autonomic innervation and alveolar formation. We also discover that planar cell polarity (PCP) signaling employs a Wnt-Fz/Ror-Vangl cascade to regulate the cytoskeleton and neurotransmitter trafficking/release from the terminals of autonomic nerves. This represents a new aspect of PCP signaling in conferring cellular properties. Together, these studies offer molecular insight into how autonomic activity controls alveolar formation. Our work also illustrates the fundamental principle of how two tissues (e.g., nerves and lungs) interact to build alveoli at the organismal level.

With age, the epidermis becomes hypoplastic and hypoproliferative. Hypoproliferation due to aging has been associated with decreased stem cell (SC) self‐renewal in multiple murine tissues. The fate of SC self‐renewal divisions can be asymmetric (one SC, one committed progenitor) or symmetric (two SCs). Increased asymmetric SC self‐renewal has been observed in inflammatory‐mediated hyperproliferation, while increased symmetric SC self‐renewal has been observed in cancers. We analyzed SC self‐renewal divisions in aging human epidermis to better understand the role of SCs in the hypoproliferation of aging. In human subjects, neonatal to 78 years, there was an age‐dependent decrease in epidermal basal layer divisions. The balance of SC self‐renewal shifted toward symmetric SC self‐renewal, with a decline in asymmetric SC self‐renewal. Asymmetric SC divisions maintain epidermal stratification, and this decrease may contribute to the hypoplasia of aging skin. P53 decreases in multiple tissues with age, and p53 has been shown to promote asymmetric SC self‐renewal. Fewer aged than adult ALDH+CD44+ keratinocyte SCs exhibited p53 expression and activity and Nutlin‐3 (a p53 activator) returned p53 activity as well as asymmetric SC self‐renewal divisions to adult levels. Nutlin‐3 increased Notch signaling (NICD, Hes1) and DAPT inhibition of Notch activation prevented Nutlin‐3 (p53)‐induced asymmetric SC self‐renewal divisions in aged keratinocytes. These studies indicate a role for p53 in the decreased asymmetric SC divisions with age and suggest that in aged keratinocytes, Notch is required for p53‐induced asymmetric SC divisions., Self‐renewal is decreased in aged human epidermis. Aging is associated with a shift in the balance of self‐renewal divisions toward increased symmetric and decreased asymmetric stem cell divisions. Fewer stem cells exhibit p53 expression and activity in aged versus young keratinocytes and p53 activation by Nutlin‐3 restores asymmetric stem cell self‐renewal divisions in aged keratinocytes.

Comprehensive and spatially mapped molecular atlases of organs at a cellular level are a critical resource to gain insights into pathogenic mechanisms and personalized therapies for diseases. The Kidney Precision Medicine Project (KPMP) is an endeavor to generate three-dimensional (3-D) molecular atlases of healthy and diseased kidney biopsies by using multiple state-of-the-art omics and imaging technologies across several institutions. Obtaining rigorous and reproducible results from disparate methods and at different sites to interrogate biomolecules at a single-cell level or in 3-D space is a significant challenge that can be a futile exercise if not well controlled. We describe a “follow the tissue” pipeline for generating a reliable and authentic single-cell/region 3-D molecular atlas of human adult kidney. Our approach emphasizes quality assurance, quality control, validation, and harmonization across different omics and imaging technologies from sample procurement, processing, storage, shipping to data generation, analysis, and sharing. We established benchmarks for quality control, rigor, reproducibility, and feasibility across multiple technologies through a pilot experiment using common source tissue that was processed and analyzed at different institutions and different technologies. A peer review system was established to critically review quality control measures and the reproducibility of data generated by each technology before their being approved to interrogate clinical biopsy specimens. The process established economizes the use of valuable biopsy tissue for multiomics and imaging analysis with stringent quality control to ensure rigor and reproducibility of results and serves as a model for precision medicine projects across laboratories, institutions and consortia.

A surge of interest has been noted in the use of mobility data from mobile phones to monitor physical distancing and model the spread of severe acute respiratory syndrome coronavirus 2, the virus that causes COVID-19. Despite several years of research in this area, standard frameworks for aggregating and making use of different data streams from mobile phones are scarce and difficult to generalise across data providers. Here, we examine aggregation principles and procedures for different mobile phone data streams and describe a common syntax for how aggregated data are used in research and policy. We argue that the principles of privacy and data protection are vital in assessing more technical aspects of aggregation and should be an important central feature to guide partnerships with governments who make use of research products.

The advent of personalized medicine has driven the development of novel approaches for obtaining detailed cellular and molecular information from clinical tissue samples. Tissue cytometry is a promising new technique that can be used to enumerate and characterize each cell in a tissue and, unlike flow cytometry and other single-cell techniques, does so in the context of the intact tissue, preserving spatial information that is frequently crucial to understanding a cell’s physiology, function, and behavior. However, the wide-scale adoption of tissue cytometry as a research tool has been limited by the fact that published examples utilize specialized techniques that are beyond the capabilities of most laboratories. Here we describe a complete and accessible pipeline, including methods of sample preparation, microscopy, image analysis, and data analysis for large-scale three-dimensional tissue cytometry of human kidney tissues. In this workflow, multiphoton microscopy of unlabeled tissue is first conducted to collect autofluorescence and second-harmonic images. The tissue is then labeled with eight fluorescent probes, and imaged using spectral confocal microscopy. The raw 16-channel images are spectrally deconvolved into 8-channel images, and analyzed using the Volumetric Tissue Exploration and Analysis (VTEA) software developed by our group. We applied this workflow to analyze millimeter-scale tissue samples obtained from human nephrectomies and from renal biopsies from individuals diagnosed with diabetic nephropathy, generating a quantitative census of tens of thousands of cells in each. Such analyses can provide useful insights that can be linked to the biology or pathology of kidney disease. The approach utilizes common laboratory techniques, is compatible with most commercially-available confocal microscope systems and all image and data analysis is conducted using the VTEA image analysis software, which is available as a plug-in for ImageJ. Tissue cytometry is a promising new microscopy technique that can be used to enumerate and characterize each cell in a tissue. Here the authors describe a complete and accessible pipeline, including methods of sample preparation, microscopy, image analysis, and data analysis for large-scale three-dimensional tissue cytometry of human kidney tissues.

Despite new advancements in surgical tools and therapies, exposure to immunosuppressive drugs related to non-immune and immune injuries can cause slow deterioration and premature failure of organ transplants. Diagnosis of these injuries by non-invasive urine monitoring would be a significant clinical advancement for patient management, especially in pediatric cohorts. We investigated the metabolomic profiles of biopsy matched urine samples from 310 unique kidney transplant recipients using gas chromatography&ndash, mass spectrometry (GC-MS). Focused metabolite panels were identified that could detect biopsy confirmed acute rejection with 92.9% sensitivity and 96.3% specificity (11 metabolites) and could differentiate BK viral nephritis (BKVN) from acute rejection with 88.9% sensitivity and 94.8% specificity (4 metabolites). Overall, targeted metabolomic analyses of biopsy-matched urine samples enabled the generation of refined metabolite panels that non-invasively detect graft injury phenotypes with high confidence. These urine biomarkers can be rapidly assessed for non-invasive diagnosis of specific transplant injuries, opening the window for precision transplant medicine.

Many economic measures are structured to reflect ethical values. I describe three attitudes towards this: maximalism, according to which we should aim to build all relevant values into measures; minimalism, according to which we should aim to keep values out of measures; and an intermediate view. I argue the intermediate view is likely correct, but existing versions are inadequate. In particular, economists have strong reason to structure measures to reflect fixed, as opposed to user-assessable, values. This implies that, despite disagreement about precisely how to do so, economists should standardly adjust QALYs and DALYs to reflect egalitarian values.

BackgroundThe kidney is a highly complex organ that performs multiple functions necessary to maintain systemic homeostasis, with complex interplay from different kidney sub-structures and the coordinated response of diverse cell types, few known and likely many others, as yet undiscovered. Traditional global sequencing techniques are limited in their ability to identify unique and functionally diverse cell types in complex tissues.MethodsHerein we characterize over 45,000 cells from 10 normal human kidneys using unbiased single-cell RNA sequencing. We also apply, for the first time, an approach of multiplexing kidney samples (Mux-Seq), pooled from different individuals, to save input sample amount and cost. We applied the computational tool Demuxlet to assess differential expression across multiple individuals by pooling human kidney cells for scRNA sequencing, utilizing individual genetic variability to determine the identity of each cell.ResultsMultiplexed droplet single-cell RNA sequencing results were highly correlated with the singleplexed sample run data. One hundred distinct cell cluster populations in total were identified across the major cell types of the kidney, with varied functional states. Proximal tubular and collecting duct cells were the most heterogeneous, displaying multiple clusters with unique ontologies. Novel proximal tubular cell subsets were identified with regenerative potential. Trajectory analysis demonstrated evolution of cell states between intercalated and principal cells in the collecting duct.ConclusionsHealthy kidney tissue has been successfully analyzed to detect all known renal cell types, inclusive of resident and infiltrating immune cells in the kidney. Mux-Seq is a unique method that allows for rapid and cost-effective single cell, in depth, transcriptional analysis of human kidney tissue.Significance StatementUse of renal biopsies for single cell transcriptomics is limited by small tissue availability and batch effects. In this study, we have successfully employed the use of Mux-Seq for the first time in kidney. Mux-Seq allows the use of single cell technology at a much more cost-effective manner by pooling samples from multiple individuals for a single sequencing run. This is even more relevant in the case of patient biopsies where the input of tissue is significantly limited. We show that the data from overlapping tissue samples are highly correlated between Mux-Seq and traditional Singleplexed RNA seq. Furthermore, the results from Mux-Seq of 4 pooled samples are highly correlated with singleplexed data from 10 singleplex samples despite the inherent variability among individuals.

Demodex mites are obligate commensal parasites of hair follicles (HF) in mammals. Normally asymptomatic, inflammatory outgrowth of mites can accompany malnutrition, immune dysfunction and aging, but mechanisms restricting Demodex outgrowth and pathogenesis are not defined. Here, we show that control over mite HF colonization of mice requires ILC2s, IL-13, and its receptor IL-4Ra, but not IL-4 or the adaptive immune system. Epithelial HF-associated ILC2s elaborate IL-13 that attenuates HF and epithelial cell proliferation at anagen onset; in their absence, Demodex colonization leads to increased epithelial proliferation and replacement of gene programs for repair by aberrant inflammatory programs leading to loss of barrier function and premature HF exhaustion over time. Humans with rhinophymatous acne rosacea, a nasal inflammatory condition associated with a high burden of Demodex, had increased HF inflammatory cells with decreased type 2 cytokines, consistent with the inverse relationship seen in mice. Our studies uncover a critical role for skin ILC2s and IL-13, which comprise an immune checkpoint necessary to sustain cutaneous integrity and restrict pathologic infestation by colonizing HF mites. This work was supported by the National Institutes of Health (AR007175 to R.R.R.G. and M.S.F, AR075880 to R.R.R.G, HL140868 to M.E.K., DK121476 to C.E.O., AI159229 to W.D., AR074556 to M.S.F., AI026918 and HL107202 to R.M.L.), Dermatology Foundation (R.R.R.G., M.S.F.), A.P. Giannini Foundation (R.R.R.G, M.E.K.), Robert Wood Johnson Foundation (R.R.R.G.), Howard Hughes Medical Institute (R.M.L.), University of California Tobacco-Related Disease Research Program (T29IP0554 to J.S.F.), and the Sandler Asthma Basic Research Center at the University of California San Francisco. R.E. Díaz was supported by NSF GRFP (#1650113). R.E. Díaz is a Howard Hughes Medical Institute Gilliam Fellow (#GT11377).

We recently reported that in humans the tetraspanin CD151 marks phenotypically distinct T cell subsets. The frequency of CD151+ T cells differs between T cell lineages and in between memory T cell populations. CD151+ T cells are hyper-proliferative and hyper-activated, as shown by phospho-proteomic analysis. We found that CD151 is an activation marker that is upregulated following TCR/CD3 activation, but at baseline, the presence of CD151 was associated with the loss of CD28 expression, a sign of T cell senescence. We hypothesized that the presence of CD151+ T cells is associated with immune hyperactivation and in extension, impaired immune surveillance. Unfortunately, we found that not even basic human CD151 T cell biology is reproduced in mouse models and thus had to resort to the study of pathological human conditions to elucidate the role(s) of CD151+ T cells. As cancer development requires immune escape, cancer diagnosis could be used as an indicator of impaired immune surveillance. Benefitting from the availability of longitudinal patient sample and data collections from people living with HIV (PLWH) we found that PLWH that developed cancer all had CD8+CD151+ T cell frequencies outside a normal reference range. CD8+CD151+ T cell frequency increase was not cancer-specific and could be detected years before the cancer diagnosis (0.5–12 years), indicating that the increase was not part of an anti-tumor response. Other established immune markers showed no correlation with the development of cancer. The findings associate elevated CD8+CD151+ T cell frequencies with impaired immune surveillance and suggest that elevated CD8+CD151+ T cell frequencies, at least in PLWH can be used as prognostic marker for cancer development. Supported by grants from NIH R01-AI122842, NIH R33-AI116188, NIH R33-AI133679