Memory Responses Research Articles

Interplays Between Matrix Metalloproteinases and Neurotropic Viruses: An Overview.

Matrix metalloproteinases (MMPs) are a diverse group of proteases involved in various physiological and pathological processes through modulation of extracellular matrix (ECM) components, cytokines, and growth factors. In the central nervous system (CNS), MMPs play a major role in CNS development, plasticity, repair, and reorganisation contributing to learning, memory, and neuroimmune response to injury. MMPs are also linked to various neurological disorders such as Alzheimer's disease, Parkinson's disease, cerebral aneurysm, stroke, epilepsy, multiple sclerosis, and brain cancer suggesting these proteases as key regulatory factors in the nervous system. Moreover, MMPs have been involved in the pathogenesis of neurotropic viral infections via dysregulation of various cellular processes, which may highlight these factors as potential targets for the treatment and control of neurological complications associated with viral pathogens. This review provides an overview of the roles of MMPs in various physiological processes of the CNS and their interactions with neurotropic viral pathogens.

Altered microstructure, phase transformation behaviors and shape memory response of CuAlMn shape memory alloys fabricated by selective laser melting

In this paper, nearly defect-free CuAlMn SMAs were successfully fabricated by selected laser melting (SLM). The result of microstructure show that only one type of thermal-induced martensite was detected in the prepared specimens, and the process parameters play a vital role in phase transformation behaviors. The alloy shows excellent ultimate tensile strength of 820 MPa and elongation of 11.5 %. Furthermore, the high shape memory response, i.e. shape recovery rate of 91.4 %–99.6 %, shape memory strain of 2.59 %–5.46 %, was presented under compressive strain not exceeding 8 %.

Object color knowledge representation occurs in the macaque brain despite the absence of a developed language system.

Animals guide their behaviors through internal representations of the world in the brain. We aimed to understand how the macaque brain stores such general world knowledge, focusing on object color knowledge. Three functional magnetic resonance imaging (fMRI) experiments were conducted in macaque monkeys: viewing chromatic and achromatic gratings, viewing grayscale images of their familiar fruits and vegetables (e.g., grayscale strawberry), and viewing true- and false-colored objects (e.g., red strawberry and green strawberry). We observed robust object knowledge representations in the color patches, especially the one located around TEO: the activity patterns could classify grayscale pictures of objects based on their memory color and response patterns in these regions could translate between chromatic grating viewing and grayscale object viewing (e.g., red grating-grayscale images of strawberry), such that classifiers trained by viewing chromatic gratings could successfully classify grayscale object images according to their memory colors. Our results showed direct positive evidence of object color memory in macaque monkeys. These results indicate the perceptually grounded knowledge representation as a conservative memory mechanism and open a new avenue to study this particular (semantic) memory representation with macaque models.

OMIP-109: 45-color full spectrum flow cytometry panel for deep immunophenotyping of the major lineages present in human peripheral blood mononuclear cells with emphasis on the T cell memory compartment.

The need for more in-depth exploration of the human immune system has moved the flow cytometry field forward with advances in instrumentation, reagent development and availability, and user-friendly implementation of data analysis methods. We developed a high-quality human 45-color panel, for comprehensive characterization of major cell lineages present in circulation including T cells, γδ T cells, NKT-like cells, B cells, NK cells, monocytes, basophils, dendritic cells, and ILCs. Assay optimization steps are described in detail to ensure that each marker in the panel was optimally resolved. In addition, we highlight the outstanding discernment of cell activation, exhaustion, memory, and differentiation states of CD4+ and CD8+ T cells using this 45-color panel. The panel enabled an in-depth description of very distinct phenotypes associated with the complexity of the T cell memory response. Furthermore, we present how this panel can be effectively used for cell sorting on instruments with a similar optical layout to achieve the same level of resolution. Functional evaluation of sorted specific rare cell subsets demonstrated significantly different patterns of immunological responses to stimulation, supporting functional and phenotypic differences within the T cell memory subsets. In summary, the combination of full spectrum profiling technology and careful assay design and optimization results in a high resolution multiparametric 45-color assay. This panel offers the opportunity to fully characterize immunological profiles present in peripheral blood in the context of infectious diseases, autoimmunity, neurodegeneration, immunotherapy, and biomarker discovery.

T Cell Responses to SARS-CoV-2 in Vaccinated Pregnant Women: A Comparative Study of Pre-Pregnancy and During-Pregnancy Infections

The COVID-19 pandemic has posed unprecedented challenges to global public health, particularly for vulnerable populations like pregnant women. This study delves into the T cell immune responses in pregnant women with confirmed SARS-CoV-2 infection, all of whom received three doses of a COVID-19 vaccine. Using the ELISpot assay, we measured T cell responses against SARS-CoV-2 spike S1 and nucleocapsid peptides in two groups: those infected before and during pregnancy. Our results showed weak to moderate correlations between T cell responses and neutralizing antibody levels, with no statistically significant differences between the two groups. T cell reactivity appeared to decrease over time post-diagnosis, regardless of infection timing. Intriguingly, over half of the participants maintained detectable T cell memory responses beyond one year post-infection, suggesting the long-term persistence of cellular immunity. These insights contribute to the understanding of COVID-19 immunology in pregnant women, highlighting the importance of considering both humoral and cellular immune responses in this high-risk population.

Humoral and cellular immune response to AZD1222 /Covishield and BV152/Covaxin COVID-19 vaccines among adults in India

ABSTRACT Several COVID-19 vaccines were developed using different approaches to prevent both symptomatic COVID-19 cases and fatalities. The adults were vaccinated with two doses of AZD1222/Covishield (n = 77) [manufactured by Serum Institute of India Pvt Ltd] vaccine and BV152/Covaxin (n = 99) [manufactured by Bharat Biotech] vaccine. They were assessed for immune response at pre-vaccination, 1 month post first and 6 months post second dose for anti-SARS-CoV-2 IgG antibody, surrogate neutralizing antibody (NAbs), immune phenotypes, antigen specific NK, B and T cell response, their effector functionality by ELISPOT and plasma cytokine profile. Both vaccines elicited enhanced IgG antibody and Nab levels compared to the baseline. BV152/Covaxin, the whole virus inactivated vaccine exhibited higher IgG (70% vs 100%), Nab (90% vs 100%), and robust T cell (31% vs 96%) responses at 6 months post second dose compared to 1 month post first dose justifying the utility of the second dose. Detection of SARS-CoV-2 WV and S1 specific CD4+ central T cell memory response in AZD1222/Covishield vaccinee at 6 months post second dose and higher CD4+ and CD8+ naïve and central memory T cell response in BV152/Covaxin vaccinee at 1 month post first dose indicated the involvement of memory T cells. Persistent IgG and NAb responses along with IgG+B and IgG+memory B cells in AZD1222/Covishield recipients at 6 months post second dose indicated sustained immune memory response. Continued heightened IFN-γ secreting T cell response (ELISPOT) displayed by both the vaccine platforms could serve as a co correlate of protection, further to evaluation in follow up studies. Overall, our data suggest that coordinated functions of humoral and cellular branches of adaptive immunity may pave ways toward protective immunity against COVID-19.

A third kind of episodic memory: Context familiarity is distinct from item familiarity and recollection.

Memory for past events is widely believed to operate through two different processes: one called 'recollection' when retrieving confident, specific details of a memory, and another called 'familiarity' when only having an unsure but conscious awareness that an item was experienced before. When people successfully retrieve details such as the source or context of a prior event, it has been assumed to reflect recollection. We demonstrate that familiarity of context is functionally distinct from familiarity of items and recollection and offer a new, tri-component model of memory. The three memory responses were differentiated across multiple behavioral and brain wave measures. What has traditionally been thought to be two kinds of memory processes are actually three, becoming evident when using sensitive enough multi-measures. Results are independently replicated across studies from different labs. These data reveal that context familiarity is a third process of human episodic memory.

Photonic Synapse of CrSBr/PtS2 Transistor for Neuromorphic Computing and Light Decoding

Abstract Field effect transistors based on 2D layered material have gained significant potential in emerging technologies, such as neuromorphic computing and ultrafast memory response for artificial intelligence applications. This study proposes a facile approach to fabricate an optoelectronic artificial synapse for neuromorphic computing and light‐decoding information system by utilizing the 2D heterostructure of CrSBr/PtS2 to overcome circuit complexity. The CrSBr layer serves as a trapping layer, while PtS2, mounted on top of CrSBr, acts as a channel layer. PtS2 exhibits n‐type semiconductor behavior with a hysteresis that varies with the thickness of the underlying CrSBr layer. The heterostructure device, featuring a 96.3 nm thick CrSBr layer, exhibited a large memory window of 11.9 V when the gate voltage is swept from −10 V to +10 V. Various synaptic behaviors are effectively demonstrated, including paired‐pulse facilitation, excitatory postsynaptic current, optical spike number and intensity‐dependent plasticity using laser light at a wavelength of 365 nm. The device achieves 26 distinct output signals depending on the intensity of the incident laser light, ranging from 10 to 385 mW cm−2, enabling its applications for light‐decoded information security systems. Thus, the investigation presents a unique approach to artificial intelligence and cybersecurity systems.

4D Printing of Multifunctional and Biodegradable PLA-PBAT-Fe3O4 Nanocomposites with Supreme Mechanical and Shape Memory Properties.

4D printing magneto-responsive shape memory polymers (SMPs) using biodegradable nanocomposites can overcome their low toughness and thermal resistance, and produce smart materials that can be controlled remotely without contact. This study presented the development of 3D/4D printable nanocomposites based on poly (lactic acid) (PLA)-poly (butylene adipate-co-terephthalate) (PBAT) blends and magnetite (Fe3O4) nanoparticles. The nanocomposites are prepared by melt mixing PLA-PBAT blends with different Fe3O4 contents (10, 15, and 20 wt%) and extruded into granules for material extrusion 3D printing. The morphology, dynamic mechanical thermal analysis (DMTA), mechanical properties, and shape memory behavior of the nanocomposites are investigated. The results indicated that the Fe3O4 nanoparticles are preferentially distributed in the PBAT phases, enhancing the storage modulus, thermal stability, strength, elongation, toughness, shape fixity, and recovery of the nanocomposites. The optimal Fe3O4 loading is found to be 10 wt%, as higher loadings led to nanoparticle agglomeration and reduced performance. The nanocomposites also exhibited fast shape memory response under thermal and magnetic activation due to the presence of Fe3O4 nanoparticles. The 3D/4D printable nanocomposites demonstrated multifunctional multi-trigger shape-memory capabilities and potential applications in contactless and safe actuation.

Bridging the gap: Insights in the immunopathology of Lyme borreliosis.

Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl) genospecies transmitted by Ixodes spp. ticks, is a significant public health concern in the Northern Hemisphere. This review highlights the complex interplay between Bbsl infection and host-immune responses, impacting clinical manifestations and long-term immunity. Early localized disease is characterized by erythema migrans (EM), driven by T-helper 1 (Th1) responses and proinflammatory cytokines. Dissemination to the heart and CNS can lead to Lyme carditis and neuroborreliosis respectively, orchestrated by immune cell infiltration and chemokine dysregulation. More chronic manifestations, including acrodermatitis chronica atrophicans and Lyme arthritis, involve prolonged inflammation as well as the development of autoimmunity. In addition, dysregulated immune responses impair long-term immunity, with compromised B-cell memory and antibody responses. Experimental models and clinical studies underscore the role of Th1/Th2 balance, B-cell dysfunction, and autoimmunity in LB pathogenesis. Moreover, LB-associated autoimmunity parallels mechanisms observed in other infectious and autoimmune diseases. Understanding immune dysregulation in LB provides insights into disease heterogeneity and could provide new strategies for diagnosis and treatment.

SARS-CoV-2 memory response in non-hospitalised cases: immunology in the context of a population-based cohort study

Background The study of non-hospitalised COVID-19 cases provides a context for improved understanding of the immune response to existing and new infections. Population-based cohorts provide a unique opportunity to do this in relation to rich longitudinal pre- and pan-pandemic data. The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992 and has subsequently followed participants for over 30 years. Methods A study comprising three clinic visits was implemented, in response to the COVID-19 pandemic, amongst ALSPAC participants to measure SARS-CoV-2 specific humoral and cellular responses longitudinally. Here we present data from the first clinic in December 2020 before the start of the UK vaccination campaign and examine associations with a set of exemplar pre- and pan-pandemic health factors. Results We observed humoral and cellular memory immune responses to SARS-CoV-2 infection in mild cases of COVID-19 up to 9 months post-infection. Symptomatic infection elicited a memory immune response of greater magnitude, though there was variation in response in both asymptomatic and symptomatic individuals. We examined health factors associated with severe COVID-19 and found that cardio-metabolomic, respiratory and immune-related health factors associate with a memory immune response of higher magnitude. For example, in older participants (mean age 58 years), higher BMI was associated with an immune memory response of greater magnitude, particularly with anti-S and anti-N binding antibodies. Conclusions We set out to illustrate the use of cohort studies to deliver detailed immunological data and to provide example analyses of how life course health factors can be examined in relation to the immune response following a widespread and novel infection. We expanded this assessment to include longitudinally assessed traits, opening up the potential for the more common use of longitudinal population studies for the better understanding the aetiology of infection outcome.

Role of SARS-CoV-2-specific memory B cells promoting immune protection after booster vaccination in solid organ transplantation.

Solid organ transplant (SOT) recipients display weak seroconversion and neutralizing antibody (NAb) responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and remain at risk of severe coronavirus disease 2019 (COVID-19). While B-cell memory is the hallmark of serological immunity, its role in driving successful vaccine responses and providing immune protection in SOT patients remains unclear. We investigated the function and interplay of SARS-CoV-2-specific memory B cells (mBc), different cytokineproducing T cells, and cross-reactive NAb in driving seroconversion and protection against COVID-19 in two cohorts. First, we studied a large cohort of 148 SOT recipients and 32 immunocompetent individuals who underwent several vaccinations. Subsequently, we assessed 25 SOT patients participating in a randomized controlled trial to compare two different immunosuppressive strategies for allowing successful seroconversion and memory-cell responses after booster vaccination. We corroborate previous findings that B- and T-cell memory responses are weaker and more delayed in SOT patients than in immunocompetent (IC) individuals; however, within the SOT cohort, we found that these responses are relatively stronger and more robust in patients not receiving mycophenolate mofetil (MMF)-based therapies. Anti- spike IgG titers strongly correlated with RBD-specific IgG-producing mBc, with both displaying broad viral cross reactivity. Prebooster SARS-CoV-2-specific mBc and IL-2- producing T cells accurately predicted Nab seroconversion (AUC, 0.828) and protection against severe COVID-19. While switching unresponsive SOT patients from calcineurin inhibitors (CNI)/MMF to a low-exposure CNI/mTOR-i regimen favored wider SARS-CoV-2-specific immune responses after a fourth booster vaccination, preformed RBD-specific mBc predicted NAb seroconversion. Our study adds new insights into the pathobiology of immune memory and highlights the pivotal role of SARS-CoV-2-specific mBc in promoting immune protection inSOT patients.

SBAC-SDN: A Scalable Blockchain-based Access Control in Northbound Interface for Multi-Controller SDN with Load Balancing Mechanism

Abstract The rapid adoption of Software-Defined Networking (SDN) has not only revolutionized network management but also presented challenges in scalability and security, particularly in multi-controller environments. This paper introduces a load balancing technique aimed at enhancing the scalability of the Northbound interface, a critical component often susceptible to performance bottlenecks. The experimental setup utilized Mininet and Ryu to create a simulated multi-controller SDN environment, where SBAC-SDN was thoroughly evaluated based on CPU and memory usage, response times, and error rates. The results showed substantial improvements in critical performance indicators, confirming the effectiveness of the load balancing technique in addressing scalability challenges. The findings indicate that the system can be scaled without excessive resource consumption, as CPU usage peaked at 60.3% and memory usage remained below 8 GB even with eight controllers. The stable average response times were consistently below 1 s, and the high throughput, ranging from 4.34 to 4.67 requests per second, further demonstrates the efficiency of the system. The error rate remained 0.0% across all configurations, highlighting the robustness of the implemented security measures. This study contributes to ongoing efforts to improve the scalability and overall robustness of SDNs, aligning with the broader goals of reliability and efficiency in network management.

8150 CD1a Lipid Presentation Contributes to T2D Phenotype in DIO Mouse Model

Abstract Disclosure: J.A. Ayala Angulo: None. K.D. Wiggins: None. M. Lopez: None. D. Nicholas: None. Type 2 Diabetes’s complex etiology, progression, and comorbidities are not fully explained by current models. Elevation of inflammatory markers and immune cell infiltration into tissues of T2D patients has been described in the literature extensively, but no clear answers as to what antigens are driving this response and how these observations contribute to disease progression exist. Recently, CD1a has been shown to present lipids to T cells and induce a memory response. Our previous work shows that T2D patients produce anti-lipid antibodies likely derived with T cell help, not present in healthy patients. Together, these data suggest a potential role for lipid-specific T cell responses to drive T2D progression through inflammatory stress, antibody production, and tissue infiltration. Current work with human CD1a transgenic B6 mice points to elevated liver steatosis and hepatitis along with higher glucose levels relative to low fat diet controls. CD1a mice show smaller islets suggesting pancreatic atrophy. This validates the CD1a-T cell mechanism as a potential contributor to T2D but also introduces a more physiologically relevant mouse model of T2D. Presentation: 6/1/2024

Aberrant cytoplasmic expression of UHRF1 restrains the MHC-I-mediated anti-tumor immune response

Immunotherapy successfully complements traditional cancer treatment. However, primary and acquired resistance might limit efficacy. Reduced antigen presentation by MHC-I has been identified as potential resistance factor. Here we show that the epigenetic regulator ubiquitin-like with PHD and ring finger domains 1 (UHRF1), exhibits altered expression and aberrant cytosolic localization in cancerous tissues, where it promotes MHC-I ubiquitination and degradation. Cytoplasmic translocation of UHRF1 is induced by its phosphorylation on a specific serine in response to signals provided by factors present in the tumor microenvironment (TME), such as TGF-β, enabling UHRF1 to bind MHC-I. Downregulation of MHC-I results in suppression of the antigen presentation pathway to establish an immune hostile TME. UHRF1 inactivation by genetic deletion synergizes with immune checkpoint blockade (ICB) treatment and induces an anti-tumour memory response by evoking low-affinity T cells. Our study adds to the understanding of UHRF1 in cancer immune evasion and provides a potential target to synergize with immunotherapy and overcome immunotherapeutic resistance.

Memory response in quasi-static thermoelastic stress in a rod due to distributed time-dependent heat sources

PurposeTo find the quasi-static thermoelastic stress and displacement, the proposed model looks at how the microstructures interact with each other and how the temperature changes inside a rod. It uses the fractional-order dual-phase-lag (FODPL) theory to derive analytical solutions for one-dimensional problems in nonsimple media within the MDD framework. The dimensionless equations are used to analyze a finite rod experiencing the heat sources continuously distributed over a finite portion of the rod which vary with time according to the ramp-type function with other sectional heat supplies kept at zero temperature. The study introduces a technique using integral transforms for exact solutions in the Laplace transform domain for different kernel functions.Design/methodology/approachA novel mathematical model incorporating dual-phase-lags, two-temperatures and Riesz space-fractional operators via memory-dependent derivatives has been established to analyze the effects of thermal stress and displacement in a finite rod. The model takes into account the continuous distribution of heat sources over a finite portion of the rod and their time variation according to the ramp-type function. It incorporates the finite Riesz fractional derivative in two-temperature thermoelasticity with dual-phase-lags via memory effect, and its solution is obtained using Laplace transform with respect to time and sine-Fourier transform with respect to spatial coordinates defined over finite domains.FindingsIn memory-dependent derivatives, thermal field variables are strongly influenced by the phase-lag heat flux and temperature gradient. The non-Fourier effects of memory-dependent derivatives substantially impact the distribution and history of the thermal field response, and energy dissipation may result in a reduction in temperature without heat transfer. The temperature, displacement and stress profile exhibit a reduced magnitude with the MDD effect compared to when the memory effect is absent (without MDD). To advance future research, a new categorization system for materials based on memory-dependent derivative parameters, in accordance with the principles of two-temperature thermoelasticity theory, must be constructed.Research limitations/implicationsThe one-dimensional assumption introduces limitations. For example, local heating of a one-dimensional plate will not extend radially, and heating one side will not heat the surrounding sides. Furthermore, while estimating heat transfer, object shape limits may apply.Originality/valueThis paper aims to revise the classical Fourier law of heat conduction and develop analytical solutions for one-dimensional problems using fractional-order dual-phase-lag (FODPL) theory in nonsimple media in the context of MDD.

Artificial olfactory memory system based on conductive metal-organic frameworks

The olfactory system can generate unique sensory memories of various odorous molecules, guiding emotional and cognitive decisions. However, most existing electronic noses remain constrained to momentary concentration, failing to trigger specific memories for different smells. Here, we report an artificial olfactory memory system utilizing conductive metal-organic frameworks (Ce-HHTP) that integrates sensing and memory and exhibits short- and long-term memory responses to alcohols and aldehydes. Experiments and theoretical calculations show that distinct memories are derived from the specific combinations of Ce-HHTP with O atoms in different guest. An unmanned aircraft equipped with this system realized the sensory memories in established areas. Moreover, the fusion of portable detection boxes and wearable flexible electrodes demonstrated the immense potential in off-site pollution monitoring and health management. This work represents an artificial olfactory memory system with two specific sensory memories under simultaneous conditions, laying the foundation for bionic design with qualities of human olfactory memory.

Maternal oral probiotic use is associated with decreased breastmilk inflammatory markers, infant fecal microbiome variation, and altered recognition memory responses in infants-a pilot observational study.

Early life gut microbiomes are important for brain and immune system development in animal models. Probiotic use has been proposed as a strategy to promote health via modulation of microbiomes. In this observational study, we explore if early life exposure to probiotics via the mother during pregnancy and lactation, is associated with decreased inflammation in breastmilk, maternal and infant microbiome variation, and altered infant neurodevelopmental features. Exclusively breastfeeding mother-infant dyads were recruited as part of the "Mothers and Infants Linked for Healthy Growth (MILk) Study." Probiotic comparison groups were defined by exposure to maternal probiotics (NO/YES) and by timing of probiotic exposure (prenatal, postnatal, total). C-reactive protein (CRP) and IL-6 levels were determined in breastmilk by immunoassays, and microbiomes were characterized from 1-month milk and from 1- and 6-month infant feces by 16S rDNA sequencing. Infant brain function was profiled via electroencephalogram (EEG); we assessed recognition memory using event-related potential (ERP) responses to familiar and novel auditory (1 month) and visual (6 months) stimuli. Statistical comparisons of study outcomes between probiotic groups were performed using permutational analysis of variance (PERMANOVA) (microbiome) and linear models (all other study outcomes), including relevant covariables as indicated. We observed associations between probiotic exposure and lower breastmilk CRP and IL-6 levels, and infant gut microbiome variation at 1- and 6-months of age (including higher abundances of Bifidobacteria and Lactobacillus). In addition, maternal probiotic exposure was associated with differences in infant ERP features at 6-months of age. Specifically, infants who were exposed to postnatal maternal probiotics (between the 1- and 6-month study visits) via breastfeeding/breastmilk, had larger differential responses between familiar and novel visual stimuli with respect to the late slow wave component of the EEG, which may indicate greater memory updating potential. The milk of mothers of this subgroup of infants had lower IL-6 levels and infants had different 6-month fecal microbiomes as compared to those in the "NO" maternal probiotics group. These results support continued research into "Microbiota-Gut-Brain" connections during early life and the role of pre- and postnatal probiotics in mothers to promote healthy microbiome-associated outcomes in infants.

Antimony Component Schottky Nanoheterojunctions as Ultrasound‐Heightened Pyroptosis Initiators for Sonocatalytic Immunotherapy

Sonocatalytic therapy (SCT) holds promise due to its exceptional penetration depth; however, the rapid recombination of electron‐hole (e−‐h+) pairs and the complex tumor microenvironment (TME) impede its broader application. Herein, we discovered that antimony (Sb)‐based nanomaterials induced pyroptosis in cancer cells. Therefore, a Schottky heterojunction containing a Sb component (Sb2Se3@Pt) was effectively designed and constructed via in‐situ growth of platinum (Pt) nanoparticles (NPs) on a Sb2Se3 semiconductor with narrow bandgaps, which were utilized as US‐heightened pyroptosis initiators to induce highly effective pyroptosis in cancer cells to boost SCT‐immunotherapy. The biological effects of the Sb2Se3@Pt nanoheterojunction itself combined with the sonocatalytic amplification of oxidative stress significantly induced Caspase‐1/GSDMD‐dependent pyroptosis in cancer cells. Therefore, SCT treatment with Sb2Se3@Pt not only effectively restrained tumor proliferation but also induced potent immune memory responses and suppressed tumor recurrence. Furthermore, the integration of this innovative strategy with immune checkpoint blockade (ICB) treatment elicited a systemic immune response, effectively augmenting therapeutic effects and impeding the growth of abscopal tumors. Overall, this study provides further opportunities to explore pyroptosis‐mediated SCT‐immunotherapy.

Abstract B034: Myeloperoxidase limits tumor-associated neutrophils mediated immunosuppression in pancreatic cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a survival rate under 12%. Treatments like immunotherapy and chemotherapy are ineffective in PDAC due to the immunosuppressive tumor microenvironment, in which tumor-associated neutrophils (TANs) are a major component. TAN immunosuppression has been shown to depend upon increased production of reactive oxygen species, with myeloperoxidase (MPO) being a major source of it. We investigated the contribution of MPO in mediating TAN immunosuppression using orthotopic PDAC models in wild-type and syngeneic MPO-deficient mice. We observed a significant delay in tumor growth and improved clinical scores when MPO was deficient. Additionally, treatment with the MPO-specific inhibitor Verdiperstat also delayed tumor growth. Flow cytometry analysis of the tumor microenvironment further confirmed a significant increase in CD8 T and NK cells, along with an increase in granzyme B level in both subsets, when MPO was deficient. Additionally, there was an increase in activation marker (CD25) and memory subset among both CD8 and CD4 T cells in MPO-deficient mice. Ex vivo studies with isolated TANs from tumor-bearing mice showed reduced CD8 T and NK cell suppression, and reactive oxygen species level in absence of MPO, supporting the contribution of MPO in TAN immunosuppression. These data suggest that loss of MPO in TANs has decreased immunosuppressive functions resulting in increased cytotoxic and activated T cells and NK cells with increased memory response within the tumor microenvironment. Our results demonstrate the contribution of MPO in regulating tumor progression, TAN immunosuppression, and immune cell infiltration using an orthotopic PDAC model. Citation Format: Angisha Basnet, Brain Boone, Tracy Liu. Myeloperoxidase limits tumor-associated neutrophils mediated immunosuppression in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B034.