Recognition of online e-cigarette marketing and e-cigarette-related attitudes and behaviors among young adults.

INTRODUCTION: Past research examining the relationship between exposure to online e-cigarette marketing and e-cigarette-related attitudes and behaviors has relied on unaided recall measures that may suffer from self-report bias. To date, few studies have presented participants with e-cigarette marketing stimuli and assessed recognition. This study examined the associations between recognition of online e-cigarette marketing stimuli and e-cigarette-related attitudes and behaviors among young adults in California. METHODS: A non-probability representative sample of young adults (ages 18-24; N=1500) living in California completed an online survey assessing their recognition of online e-cigarette marketing stimuli, including image-based (i.e., Instagram, email) and audiovisual (i.e., YouTube, TikTok) promotions, and positive e-cigarette-related attitudes (e.g., appeal of e-cigarettes) and behaviors (e.g., e-cigarette use). Adjusted and weighted logistic regression analyses were used. RESULTS: 79.0% (n=1185) of young adults, including 78.1% (n=310/397) of participants under 21 years old, recognized online e-cigarette marketing. Participants who reported recognition of stimuli, compared with those who did not, had greater odds of reporting appeal of e-cigarettes (AOR=2.26, 95% CI=1.65-3.09) and e-cigarette purchase intentions (AOR=1.66, 95% CI=1.13-2.43) among all participants, and susceptibility to use e-cigarettes among never users (AOR=2.29, 95% CI=1.59-3.29). CONCLUSIONS: Young adults in California recognized audiovisual and image-based online e-cigarette marketing. Such recognition may lead to positive e-cigarette-related attitudes and behavioral intentions, especially among never users. Future research should examine the causal relationship between the associations found in this study. Findings may inform the development and evaluation of psychometrically valid measures of online e-cigarette marketing exposures. IMPLICATIONS: Recognition of online e-cigarette marketing stimuli was associated with greater odds of reporting appeal and benefits of e-cigarettes, purchase intentions, and lifetime e-cigarette use among all participants, and susceptibility to use e-cigarettes among never users. These findings may motivate the development and evaluation of psychometrically valid measures of online e-cigarette marketing exposures.

Perspectives of people with spinal cord injury on a pain education resource.

Introduction: Spinal cord injury (SCI) often leads to neuropathic pain that negatively affects quality of life. Several qualitative research studies in individuals with SCI who experience neuropathic pain indicate the lack of adequate information about pain. We previously developed an educational resource, the SeePain, based on scientific literature and a series of qualitative interviews of people with SCI, their significant others/family members, and SCI healthcare providers. Methods: However, to quantitatively evaluate the utility of this educational resource in a larger sample, we examined the agreement and usefulness ratings of statements regarding clarity/comprehensibility, content, and format of the SeePain, derived from the thematic analysis of our previous qualitative interviews. Participants completed a survey that provided a digital version of the SeePain and then rated their agreement/usefulness with the statements using numerical rating scales. Results: There were overall high perceived agreement and usefulness ratings regarding the SeePain's clarity, content, and format. A factor analysis reduced the agreement and usefulness ratings into 4 components (content, clarity, format, and delivery medium). Group comparisons showed that individuals with higher education were more likely to endorse electronic and website formats, and the usefulness of a shorter version of the SeePain; females and younger individuals showed greater endorsement for clarity. Finally, higher pain intensity ratings were associated with greater agreement and usefulness of the content of the SeePain. Discussion: Overall, these results support the utility of the SeePain as a source of information regarding pain that may facilitate communication about pain and its management following SCI.

UCP1 expression in human brown adipose tissue is inversely associated with cardiometabolic risk factors.

OBJECTIVE: Brown adipose tissue (BAT) is a therapeutic target for obesity. 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is commonly used to quantify human BAT mass and activity. Detectable 18F-FDG uptake by BAT is associated with reduced prevalence of cardiometabolic disease. However, 18F-FDG uptake may not always be a reliable marker of BAT thermogenesis, for example insulin resistance may reduce glucose uptake. Uncoupling protein 1 (UCP1) is the key thermogenic protein in BAT. Therefore, we hypothesized that UCP1 expression may be altered in individuals with cardiometabolic risk factors. METHODS: We quantified UCP1 expression as an alternative marker of thermogenic capacity in BAT and white adipose tissue (WAT) samples (n = 53) and in differentiated brown and white pre-adipocytes (n = 85). RESULTS: UCP1 expression in BAT, but not in WAT or brown/white differentiated pre-adipocytes, was reduced with increasing age, obesity and adverse cardiometabolic risk factors such as fasting glucose, insulin and blood pressure. However, UCP1 expression in BAT was preserved in obese subjects of <40 years of age. To determine if BAT activity was also preserved in vivo, we undertook a case-control study, performing 18F-FDG scanning during mild cold exposure in young (mean age ∼22y) normal weight and obese volunteers. 18F-FDG uptake by BAT and BAT volume were similar between groups, despite increased insulin resistance. CONCLUSION: 18F-FDG uptake by BAT and UCP1 expression are preserved in young obese adults. Older subjects retain precursor cells with the capacity to form new thermogenic adipocytes. These data highlight the therapeutic potential of BAT mass expansion and activation in obesity.

T Cell Exhaustion Markers in Multiple Myeloma Patients are Lower After Physical Activity Intervention.

PURPOSE: There is compelling evidence that CD4+ and CD8+T cells are dysfunctional in multiple myeloma, compromising their ability to control disease progression. Pre-clinical models suggest that exercise represents a non-pharmacologic means to reduce immune exhaustion, but no studies to date have examined the relationship between an exercise intervention and biomarkers of immune exhaustion in multiple myeloma patients. PATIENTS AND METHODS: The current study includes 24 multiple myeloma patients who participated in a six-month physical activity intervention, consisting of supervised strength training (n = 12) and unsupervised home-based walking arms (n = 12). Comprehensive flow cytometry was utilized to assess the frequency of CD4+ and CD8+T cells and subpopulations expressing the markers of exhaustion PD-1, TIGIT, TIM3 and/or LAG3. Ratios of exhausted to non-exhausted cell populations, and percentages of exhausted to total populations of the same lineage, were calculated for the baseline and final timepoints. RESULTS: Eighteen of 20 exhaustion measures were lower at the end of the intervention than at baseline, and several were significantly or borderline significantly reduced in the entire sample or in one of the arms. The entire sample saw improvements in the ratios of CD4+ TIGIT+ to non-exhausted CD4+ (0.7 [0.6] to 0.6 [0.4], P = .04) and CD8+ PD1+ to non-exhausted CD8+ (1.8 [2.6] to 1.5 [2.0], P = .06), and in total exhausted CD8+ as a percent of total CD8+ (72.9 [21.9] to 68.3 [19.6], P < .01). CONCLUSIONS: This pilot study suggests that physical activity induces changes in MM patients' immune systems, potentially rendering a less exhausted T cell state.

CD163+ macrophages in the triple-negative breast tumor microenvironment are associated with improved survival in the Women's Circle of Health Study and the Women's Circle of Health Follow-Up Study.

BACKGROUND: Tumor-associated macrophages (TAMs) are a prominent immune subpopulation in the tumor microenvironment that could potentially serve as therapeutic targets for breast cancer. Thus, it is important to characterize this cell population across different tumor subtypes including patterns of association with demographic and prognostic factors, and breast cancer outcomes. METHODS: We investigated CD163+ macrophages in relation to clinicopathologic variables and breast cancer outcomes in the Women's Circle of Health Study and Women's Circle of Health Follow-up Study populations of predominantly Black women with breast cancer. We evaluated 611 invasive breast tumor samples (507 from Black women, 104 from White women) with immunohistochemical staining of tissue microarray slides followed by digital image analysis. Multivariable Cox proportional hazards models were used to estimate hazard ratios for overall survival (OS) and breast cancer-specific survival (BCSS) for 546 cases with available survival data (median follow-up time 9.68 years (IQR: 7.43-12.33). RESULTS: Women with triple-negative breast cancer showed significantly improved OS in relation to increased levels of tumor-infiltrating CD163+ macrophages in age-adjusted (Q3 vs. Q1: HR = 0.36; 95% CI 0.16-0.83) and fully adjusted models (Q3 vs. Q1: HR = 0.30; 95% CI 0.12-0.73). A similar, but non-statistically significant, association was observed for BCSS. Macrophage infiltration in luminal and HER2+ tumors was not associated with OS or BCSS. In a multivariate regression model that adjusted for age, subtype, grade, and tumor size, there was no significant difference in CD163+ macrophage density between Black and White women (RR = 0.88; 95% CI 0.71-1.10). CONCLUSIONS: In contrast to previous studies, we observed that higher densities of CD163+ macrophages are independently associated with improved OS and BCSS in women with invasive triple-negative breast cancer. Trial registration Not applicable.

TIST-Net: style transfer in dynamic contrast enhanced MRI using spatial and temporal information.

Objective.Training deep learning models for image registration or segmentation of dynamic contrast enhanced (DCE) MRI data is challenging. This is mainly due to the wide variations in contrast enhancement within and between patients. To train a model effectively, a large dataset is needed, but acquiring it is expensive and time consuming. Instead, style transfer can be used to generate new images from existing images. In this study, our objective is to develop a style transfer method that incorporates spatio-temporal information to either add or remove contrast enhancement from an existing image.Approach.We propose a temporal image-to-image style transfer network (TIST-Net), consisting of an auto-encoder combined with convolutional long short-term memory networks. This enables disentanglement of the content and style latent spaces of the time series data, using spatio-temporal information to learn and predict key structures. To generate new images, we use deformable and adaptive convolutions which allow fine grained control over the combination of the content and style latent spaces. We evaluate our method, using popular metrics and a previously proposed contrast weighted structural similarity index measure. We also perform a clinical evaluation, where experts are asked to rank images generated by multiple methods.Main Results.Our model achieves state-of-the-art performance on three datasets (kidney, prostate and uterus) achieving an SSIM of 0.91 ± 0.03, 0.73 ± 0.04, 0.88 ± 0.04 respectively when performing style transfer between a non-enhanced image and a contrast-enhanced image. Similarly, SSIM results for style transfer from a contrast-enhanced image to a non-enhanced image were 0.89 ± 0.03, 0.82 ± 0.03, 0.87 ± 0.03. In the clinical evaluation, our method was ranked consistently higher than other approaches.Significance.TIST-Net can be used to generate new DCE-MRI data from existing images. In future, this may improve models for tasks such as image registration or segmentation by allowing small training datasets to be expanded.

Content analysis of email marketing communications among online e-cigarette retailers.

INTRODUCTION: Online e-cigarette retailers use email communications to promote products directly to consumers, which may facilitate e-cigarette use. Little is known about the content of these emails. As such, this study collected emails from online e-cigarette retailers in California to conduct a content analysis. METHODS: This study included 13 online e-cigarette retailers in California using Yelp. To be included in the study, e-cigarette retailers needed a live website, physical retail location (i.e., vape shop), and e-cigarettes available for purchase online. The research team entered each website and signed up (if possible) for an email newsletter. Data were collected from the Gmail Application Programming Interface over a 1-year study period (11/01/21-11/01/22). Members of the research team coded emails for the presence of e-cigarettes, other products, flavors, marketing categories, and promotional activities, among other variables. RESULTS: 749 promotional emails (2.1 avg/per day) were received over the 1-year study period. Second-generation e-cigarettes (n=581, 77.6%) were the most observed product in emails followed by disposable e-cigarettes (n=391, 52.2%). The most common flavor profile was fruit/sweet/liquor (n=424, 56.6%). Emails included links to social media pages (n=366, 48.9%). Online coupons were found in 53.1% (n=398) of the emails. Age warnings were displayed in 8.0% (n=60) of the emails. CONCLUSIONS: E-cigarette retailers' emails promoted new products, flavors, and contained promotional discounts. Future research should examine the impact of exposure to such emails on e-cigarette-related attitudes and behaviors. IMPLICATIONS: Findings from this study may help inform prevention programs and interventions focused on increasing tobacco-related digital media literacy (i.e., evaluate tobacco advertising messages on digital media) among gender and ethnic minorities. Future research should examine if exposure to email marketing is causally linked with e-cigarette use among gender and ethnic minorities.

Identification of Enhanced Vaccine Mimotopes for the p15E Murine Cancer Antigen.

Mimotopes of short CD8+ T-cell epitopes generally comprise one or more mutated residues, and can increase the immunogenicity and function of peptide cancer vaccines. We recently developed a two-step approach to generate enhanced mimotopes using positional peptide microlibraries and herein applied this strategy to the broadly used H-2Kb-restricted murine leukemia p15E tumor rejection epitope. The wild-type p15E epitope (sequence: KSPWFTTL) was poorly immunogenic in mice, even when combined with a potent peptide nanoparticle vaccine system and did not delay p15E-expressing MC38 tumor growth. Following positional microlibrary functional screening of over 150 mimotope candidates, two were identified, both with mutations at residue 3 (p15E-P3C; "3C," and p15E-P3M; "3M") that better induced p15E-specific CD8+ T cells and led to tumor rejection. Although 3M was more immunogenic, 3C effectively delayed tumor growth in a therapeutic setting relative to the wild-type p15E. As 3C had less H-2Kb affinity relative to both p15E and 3M, 15 additional mimotope candidates (all that incorporated the 3C mutation) were assessed that maintained or improved predicted MHC-I affinity. Valine substitution at position 2 (3C2V, sequence: KVCWFTTL) led to improved p15E-specific immunogenicity, tumor rejection, and subsequent long-term antitumor immunity. 3C, 3M, and 3C2V mimotopes were more effective than p15E in controlling MC38 and B16-F10 tumors. T-cell receptor (TCR) sequencing revealed unique TCR transcripts for mimotopes, but there were no major differences in clonality. These results provide new p15E mimotopes for further vaccine use and illustrate considerations for MHC-I affinity, immunogenicity, and functional efficacy in mimotope design. SIGNIFICANCE: The MHC-I-restricted p15E tumor rejection epitope is expressed in multiple murine cancer lines and is used as a marker of antitumor cellular immunity, but has seen limited success as a vaccine immunogen. An in vivo screening approach based on a positional peptide microlibraries is used to identify enhanced p15E mimotopes bearing amino acid mutations that induce significantly improved functional immunogenicity relative to vaccination with the wild-type epitope.

Clinical and radiological septic joint analysis of spontaneous sternoclavicular joint infections: achieving the best outcomes-a systems engineering approach.

OBJECTIVES: Spontaneous sternoclavicular joint infection (SSCJI) is a rare and poorly understood disease process. This study aims to identify factors guiding effective management strategies for SSCJI by using data mining. METHODS: An Institutional Review Board-approved retrospective review of patients from 2 large hospitals (2010-2022) was conducted. SSCJI is defined as a joint infection without direct trauma or radiation, direct instrumentation or contiguous spread. An interdisciplinary team consisting of thoracic surgeons, radiologists, infectious disease specialists, orthopaedic surgeons, hospital information experts and systems engineers selected relevant variables. Small set data mining algorithms, utilizing systems engineering, were employed to assess the impact of variables on patient outcomes. RESULTS: A total of 73 variables were chosen and 54 analysed against 11 different outcomes. Forty-seven patients [mean age 51 (22-82); 77% male] met criteria. Among them, 34 underwent early joint surgical resection (<14 days), 5 patients received delayed surgical intervention (>14 days) and 8 had antibiotic-only management. The antibiotic-only group had comparable outcomes. Indicators of poor outcomes were soft tissue fluid >4.5 cm, previous SSCJI, moderate/significant bony fragments, HgbA1c >13.9% and moderate/significant bony sclerosis. CONCLUSIONS: This study suggests that targeted antibiotic-only therapy should be considered initially for SSCJI cases while concurrently managing comorbidities. Patients displaying indicators of poor outcomes or no symptomatic improvement after antibiotic-only therapy should be considered for surgical joint resection.

Aryl hydrocarbon receptor suppresses STING-mediated type I IFN expression in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is one of the most aggressive types of cancer. Despite decades of intense investigation, treatment options remain limited, and rapid recurrence with distant metastases remains a significant challenge. Cancer cell-intrinsic production of cytokines such as type I interferons (IFN-I) is a known potent modulator of response to therapy in many cancers, including TNBC, and can influence therapeutic outcome. Here, we report that, in TNBC systems, the aryl hydrocarbon receptor (AhR) suppresses IFN-I expression via inhibition of STImulator of Interferon Genes (STING), a key mediator of interferon production. Intratumoral STING activity is essential in mediating the efficacy of PARP inhibitors (PARPi) which are used in the treatment of cancers harboring BRCA1 deficiency. We find that, in TNBC cells, PARPi treatment activates AhR in a BRCA1 deficiency-dependent manner, thus suggesting the presence of a negative feedback loop aimed at modulating PARPi efficacy. Importantly, our results indicate that the combined inhibition of PARP and AhR is superior in elevating IFN-I expression as compared to PARPi-alone. Thus, AhR inhibition may allow for enhanced IFN-I production upon PARPi in BRCA1-deficient breast cancers, most of which are of TNBC origin, and may represent a therapeutically viable strategy to enhance PARPi efficacy.

Neutrophil Granulopoiesis Optimized Through Ex Vivo Expansion of Hematopoietic Progenitors in Engineered 3D Gelatin Methacrylate Hydrogels.

Neutrophils are the first line of defense of the innate immune system. In response to methicillin-resistant Staphylococcus aureus infection in the skin, hematopoietic stem, and progenitor cells (HSPCs) traffic to wounds and undergo extramedullary granulopoiesis, producing neutrophils necessary to resolve the infection. This prompted the engineering of a gelatin methacrylate (GelMA) hydrogel that encapsulates HSPCs within a matrix amenable to subcutaneous delivery. The authors study the influence of hydrogel mechanical properties to produce an artificial niche for granulocyte-monocyte progenitors (GMPs) to efficiently expand into functional neutrophils that can populate infected tissue. Lin-cKIT+ HSPCs, harvested from fluorescent neutrophil reporter mice, are encapsulated in GelMA hydrogels of varying polymer concentration and UV-crosslinked to produce HSPC-laden gels of specific stiffness and mesh sizes. Softer 5% GelMA gels yield the most viable progenitors and effective cell-matrix interactions. Compared to suspension culture, 5% GelMA results in a twofold expansion of mature neutrophils that retain antimicrobial functions including degranulation, phagocytosis, and ROS production. When implanted dermally in C57BL/6J mice, luciferase-expressing neutrophils expanded in GelMA hydrogels are visualized at the site of implantation for over 5 days. They demonstrate the potential of GelMA hydrogels for delivering HSPCs directly to the site of skin infection to promote local granulopoiesis.

Downregulation of IRF8 in alveolar macrophages by G-CSF promotes metastatic tumor progression.

Tissue-resident macrophages (TRMs) are abundant immune cells within pre-metastatic sites, yet their functional contributions to metastasis remain incompletely understood. Here, we show that alveolar macrophages (AMs), the main TRMs of the lung, are susceptible to downregulation of the immune stimulatory transcription factor IRF8, impairing anti-metastatic activity in models of metastatic breast cancer. G-CSF is a key tumor-associated factor (TAF) that acts upon AMs to reduce IRF8 levels and facilitate metastasis. Translational relevance of IRF8 downregulation was observed among macrophage precursors in breast cancer and a CD68hiIRF8loG-CSFhi gene signature suggests poorer prognosis in triple-negative breast cancer (TNBC), a G-CSF-expressing subtype. Our data highlight the underappreciated, pro-metastatic roles of AMs in response to G-CSF and identify the contribution of IRF8-deficient AMs to metastatic burden. AMs are an attractive target of local neoadjuvant G-CSF blockade to recover anti-metastatic activity.

Associations between executive functions assessed in different contexts in a genetically informative sample.

Executive functions (EFs) are cognitive functions that help direct goal-related behavior. EFs are usually measured via behavioral tasks assessed in highly controlled laboratory settings under the supervision of a research assistant. Online versions of EF tasks are an increasingly popular alternative to in-lab testing. However, researchers do not have the same control over the testing environment during online EF assessments. To assess the extent to which EFs assessed in-lab and online are related, we used data from the Colorado Online Twin Study (CoTwins; 887 individual twins aged 13.98-19.05) and constructed an Lab Common EF factor and an Online Common EF factor from four EF tasks assessed in-lab and online. The Lab Common and Online Common EF factors were genetically identical (rA = 1.00) but phenotypically separable (r = .77, 95% confidence interval [0.59, 0.94]) indicating that these EF factors have the same genetic underpinnings but may be differentially influenced by environmental factors. We examined phenotypic, genetic, and environmental correlations between the EF factors and a general cognitive ability factor (g) assessed in the lab and found similar relationships between Lab Common EF and g and Online Common EF and g. Overall, these results suggest that Common EF factors assessed in different contexts are highly related to each other and similarly related to other cognitive outcomes. These findings indicate that online task-based EF assessments could be a viable strategy for increasing sample sizes in large-scale studies, particularly genetically informed studies. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Examining Tobacco-Related Social Media Research in Government Policy Documents: Systematic Review.

BACKGROUND: Social media data have been used to describe tobacco industry marketing practices, user experiences with tobacco, and youth-oriented protobacco content. OBJECTIVE: Examine the extent to which tobacco-related social media research is cited in government policy documents. SEARCH METHODS: Peer-reviewed tobacco-related social media studies were searched for on Web of Science, PubMed, and other databases from 2004 to 2022. The DOI number for each identified article was then used to search the Overton database to find policy documents citing such research. A secondary, manual search of national and international governmental agency websites was also conducted. SELECTION CRITERIA: Documents were included in this study if they were tobacco-related, written in English, cited social media research in the document text and reference section, and were published by a governmental office or agency. DATA COLLECTION AND ANALYSIS: The analytic sample consisted of (n = 38) government policy documents, and were coded for content themes, agency type, document type, and subsequent citations. MAIN RESULTS: When this research was utilized, it was often in the context of highlighting tobacco industry marketing practices, bringing attention to an issue (eg, youth e-cigarette use), and/or describing how social media platforms can be used as a data source to understand tobacco-related attitudes and behaviors. Agencies that often cited this research were the WHO, FDA, and CDC. The document types included research reports, policy recommendations, industry guidance, legal complaints, and practice-based recommendations. CONCLUSIONS: Tobacco-related social media research has been utilized by government agencies in the last decade to guide the policy process. IMPLICATIONS: Tobacco-related social media research has been used in government policy documents to detail tobacco industry marketing and bring attention to youth exposure to protobacco content online. Continued surveillance of social media may be necessary to track the changing tobacco landscape.

Examining the Peer-Reviewed Literature on Tobacco-Related Social Media Data: Scoping Review.

INTRODUCTION: Tobacco researchers have used social media data to examine tobacco industry marketing practices (eg, influencers), and to document user experience with tobacco products. This study summarized the literature that analyzed tobacco-related social media data, including domain, social media platform, tobacco product type, and themes of findings, among other variables. AIMS AND METHODS: PubMed, PsycINFO, Web of Science, and Communication Source were searched between 2004 and 2022. Peer-reviewed articles were included if they were written in English, included at least one tobacco-related term, and one social media-related term, and analyzed a social media post. Two coders screened all-titles and abstracts. The final sample consisted of (n = 255) articles. Studies were coded for domain, social media platform, tobacco product type, data source, type of data, coding and analytic method, and presence of validation procedure, among other variables. RESULTS: A total of 10 504 820 581 tobacco-related social media posts were assessed across 255 studies. User experience (54.1%) and promotion (23.1%) were the most researched domains. Researchers used data from Twitter the most (42.7%). Text (43.1%) was the most common type of data analyzed. Thematic analysis (80.8%) was the most common analytic technique. Themes of findings from content analyses often pertained to the health effects of tobacco use (61.0%) and promotion (44.2%). CONCLUSIONS: Researchers have analyzed billions of tobacco-related social media posts to describe user experience with, and promotions related to, tobacco products like e-cigarettes on platforms like Twitter. Future research may examine tobacco-related social media data from newer platforms like TikTok. IMPLICATIONS: Real-time surveillance of tobacco-related content on social media can keep the tobacco control community abreast of tobacco industry promotional strategies, user experience with tobacco products, and perceived health effects of tobacco use. A framework may be developed to establish best-practices for social media data collection and analysis, including strategies to identify posts from bot accounts and validate methodological approaches used in thematic analysis.

A Bacterial and Ganglioside-based Nanoparticle Initiates Reprogramming of Macrophages and Promotes Antitumor Phenotypes.

Macrophages represent the most abundant immune component of the tumor microenvironment and often exhibit protumorigenic (M2-like) phenotypes that contribute to disease progression. Despite their generally accepted protumorigenic role, macrophages can also display tumoricidal (or M1-like) behavior, revealing that macrophages can be functionally reprogrammed, depending on the cues received within the tumor microenvironment. Moreover, such plasticity may be achieved by pharmacologic or biologic interventions. To that end, we previously demonstrated that a novel immunomodulator termed the "very small size particle" (VSSP) facilitates maturation of dendritic cells and differentiation of myeloid-derived suppressor cells to APCs with reduced suppressive activity in cancer models. VSSP was further shown to act in the bone marrow to drive the differentiation of progenitors toward monocytes, macrophages, and dendritic cells during emergency myelopoiesis. However, the underlying mechanisms for VSSP-driven alterations in myeloid differentiation and function remained unclear. In this study, in mouse models, we focused on macrophages and tested the hypothesis that VSSP drives macrophages toward M1-like functional states via IRF8- and PU.1-dependent mechanisms. We further hypothesized that such VSSP-mediated actions would be accompanied by enhanced antitumor responses. Overall, we showed that (1) VSSP drives naive or M2-derived macrophages to M1-like states, (2) the M1-like state induced by VSSP occurs via IRF8- and PU.1-dependent mechanisms, and (3) single-agent VSSP induces an antitumor response that is accompanied by alterations in the intratumoral myeloid compartment. These results provide a deeper mechanistic underpinning of VSSP and strengthen its use to drive M1-like responses in host defense, including cancer.