Illumination Area Research Articles

Tunable photo-response in the visible to NIR spectrum range of Germanium-based junctionless nanowire transistor.

In this paper, the phototransistor behavior is investigated in the germanium-on-insulator (GeOI)-based junctionless nanowire (JL-NW) transistor under various light conditions. High responsivity and photosensitivity are attributed in the fully depleted regime within the visible and near-infrared bands. The impact of light is also investigated in detail on the electronic and transfer characteristics such as energy bandgap, carrier distribution, electrostatic potential, electric field, and generation and recombination rates. Further, the channel doping and thickness are tuned to optimize the optical responsivity. The significant tunability of responsivity is observed with increasing channel thickness. The device exhibits fast optical switching performance, which is further enhanced at higher input light power. Overall, at the nanoscale dimension, our proposed phototransistor demonstrates better detectivity with a significantly smaller illumination area. Thus, the GeOI-based JL-NW phototransistors can be used for imaging (visible wavelength range) and bioimaging (near-infrared wavelength range) applications in advanced technology nodes.

Raman spectroscopic quantification of polyethylene particles in water using polydimethylsiloxane-coated nickel foam as a particle-capturing platform

Nickel foam (NF) was evaluated as a medium for the capture of polyethylene (PE) particles in water. NF is a hydrophobic and porous material with a large surface area, making it a promising candidate for attracting PE particles. However, the particle-capturing efficiency using bare NF was only 69.5%. To increase capturing efficiency, a circular polydimethylsiloxane (PDMS)-coated NF (PDMS@NF, diameter: 6 mm) was employed to enhance the hydrophobicity. The capturing efficiency using the PDMS@NF was substantially increased to 97.6 % owing to the increase in hydrophobicity. To quantify the captured PE particles on/in the PDMS@NF using Raman spectroscopy, a wide area illumination (WAI) scheme providing 6 mm-diameter laser illumination was adopted to fully cover the PDMS@NF for representative spectroscopic sampling and accurate quantification. The intensity ratios of PE to PDMS peaks in the collected spectra clearly increased with the quantity of dispersed PE particles (0.1 ∼ 4.0 mg range, R2: 0.992) in the water samples, and the limit of detection was 0.08 mg. Moreover, the capturing efficiencies for polypropylene (PP), polystyrene (PS), and polyethylene terephthalate (PET) particles (1 mg of each) using the PDMS@NF were also superior, ranging from 96.4 to 98.2 %. Therefore, the proposed scheme incorporating the PDMS@NF as a particle-capturing and Raman measurement platform has potential as a method for on-line detection of microplastics in water.

Spatial Profiling of Ovarian Clear Cell Carcinoma Reveals Immune-Hot Features

Ovarian clear cell carcinoma (OCCC) has a high incidence in Asia, with a frequent occurrence at an early stage, but without sufficient data on molecular stratification for high-risk patients. Recently, immune-hot features have been proposed as indicators of poor prognosis in early stage OCCC. Specific patterns of intratumoral heterogeneity associated with immune-hot features must be defined. NanoString Digital Spatial Profiling technology was used to decipher the spatial distribution of the 18-plex protein panel. Regions of interest (ROIs) were collected based on the reference hematoxylin and eosin–stained morphology. Areas of illumination (AOIs) were defined according to the ROI segmentation using the fluorescence signals of the visualization markers pan-cytokeratin (PanCK), CD45, or DNA. Unsupervised hierarchical clustering of 595 AOIs from 407 ROIs showed that the PanCK segments expressed different combinations of immune markers, suggestive of immune mimicry. The following 3 immune-hot clusters were identified: granzyme B–high, immune signal-high , and immune-like cells; the following 2 immune-cold clusters were identified: fibronectin-high and immune checkpoint–high cells. In tumor samples at the International Federation of Gynecology and Obstetrics stage IC1/2 experiencing recurrence, there was an increased occurrence of PanCK+ AOIs with immune signal-high and immune-like cell groups in the papillary morphology surrounded by macrophage lineage tumor-infiltrating immune cells (TIIs). In contrast, for tumor samples at the International Federation of Gynecology and Obstetrics stage IC3/II with recurrence, PanCK+ AOIs were prevalent in the fibronectin-high group, particularly in those with a tubulocystic morphology surrounded by lymphoid lineage non-TIIs. Our study on the spatial profiling of early stage OCCC tumors revealed that the immune mimicry of tumor cells, presence of TIIs, and morphologic patterns were associated with recurrence, which switched during tumor progression.

Synthesis, Development, and Evaluation Technologies of High-quality Quantum Dots

Reliable quantum dots are prerequisite to the development of quantum device assembly. It may serve as a single photon source that can be combined with the rest of the assembly for the delivery of the generated photon. This article briefly introduces the synthesis, development and evaluation technologies of high-quality quantum dots. Their applications in display and illumination areas in the form of remote components will also be briefly introduced.

Three-Dimensional Reconstruction of Indoor Scenes Based on Implicit Neural Representation.

Reconstructing 3D indoor scenes from 2D images has always been an important task in computer vision and graphics applications. For indoor scenes, traditional 3D reconstruction methods have problems such as missing surface details, poor reconstruction of large plane textures and uneven illumination areas, and many wrongly reconstructed floating debris noises in the reconstructed models. This paper proposes a 3D reconstruction method for indoor scenes that combines neural radiation field (NeRFs) and signed distance function (SDF) implicit expressions. The volume density of the NeRF is used to provide geometric information for the SDF field, and the learning of geometric shapes and surfaces is strengthened by adding an adaptive normal prior optimization learning process. It not only preserves the high-quality geometric information of the NeRF, but also uses the SDF to generate an explicit mesh with a smooth surface, significantly improving the reconstruction quality of large plane textures and uneven illumination areas in indoor scenes. At the same time, a new regularization term is designed to constrain the weight distribution, making it an ideal unimodal compact distribution, thereby alleviating the problem of uneven density distribution and achieving the effect of floating debris removal in the final model. Experiments show that the 3D reconstruction effect of this paper on ScanNet, Hypersim, and Replica datasets outperforms the state-of-the-art methods.

Illumination-adjustable photoacoustic and harmonic ultrasound for tracking magnetically driven microrobots.

The development of microrobots for biomedical applications has enabled tasks such as targeted drug delivery, minimally invasive surgeries, and precise diagnostics. However, effective in vivo navigation and control remain challenging due to their small size and complex body environment. Photoacoustic (PA) and ultrasound (US) imaging techniques, which offer high contrast, high resolution, and deep tissue penetration, are integrated to enhance microrobot visualization and tracking. Traditional imaging systems have a narrow effective illumination area, suffer from severe reflection artifacts, and are affected by strong electromagnetic fields. To address this, we present an illumination-adjustable PA and harmonic US imaging system with a customized pushrod mechanism for real-time focus adjustment. Experiments demonstrate high-resolution imaging and accurate microrobot positioning, showcasing the potential for biomedical applications, especially in minimally invasive procedures.

A Novel SAR Imaging Method for GEO Satellite–Ground Bistatic SAR System with Severe Azimuth Spectrum Aliasing and 2-D Spatial Variability

The satellite–ground bistatic configuration, which uses geosynchronous synthetic aperture radar (GEO SAR) for illumination and ground equipment for reception, can achieve wide coverage, high revisit, and continuous illumination of interest areas. Based on the analysis of the signal characteristics of GEO satellite–ground bistatic SAR (GEO SG-BiSAR), it is found that the bistatic echo signal has problems of azimuth spectrum aliasing and 2-D spatial variability. Therefore, to overcome those problems, a novel SAR imaging method for a GEO SG-BiSAR system with severe azimuth spectrum aliasing and 2-D spatial variability is proposed. Firstly, based on the geometric configuration of the GEO SG-BiSAR system, the time-domain and frequency-domain expressions of the signal are derived in detail. Secondly, in order to avoid the increasing cost caused by traditional multi-channel reception technology and the processing burden caused by inter-channel errors, the azimuth deramping is executed to solve the azimuth spectrum aliasing of the signal under the special geometric structure of GEO SG-BiSAR. Thirdly, based on the investigation of azimuth and range spatial variability characteristics of GEO SG-BiSAR in the Range Doppler (RD) domain, the azimuth spatial variability correction strategy is proposed. The signal corrected by the correction strategy has the same migration characteristics as monostatic radar. Therefore, the traditional chirp scaling function (CSF) is also modified to solve the range spatial variability of the signal. Finally, the two-dimensional spectrum of GEO SG-BiSAR with modified chirp scaling processing is derived, followed by the SPECAN operation to obtain the focused SAR image. Furthermore, the completed flowchart is also given to display the main composed parts for GEO SG-BiSAR imaging. Both azimuth spectrum aliasing and 2-D spatial variability are taken into account in the imaging method. The simulated data and the real data obtained by the Beidou navigation satellite are used to verify the effectiveness of the proposed method.

Retinal Pigment Epithelium and Outer Retinal Atrophy (RORA) in Retinitis Pigmentosa: Functional, Structural, and Genetic Evaluation.

To examine whether the extension of retinal pigment epithelium (RPE) and outer retinal atrophy (RORA) and various other morphofunctional parameters correlate with the genetic assessment and severity of retinitis pigmentosa (RP). Thirty-eight patients (76 eyes) with RP were prospectively enrolled and underwent full ophthalmic examination, including visual field testing, full-field electroretinography (ERG), and optical coherence tomography angiography. The severity of the disease was calculated using the RP stage scoring system, and the area of RORA was assessed using the automatically calculated area of sub-RPE illumination. Blood or saliva samples were collected from subjects, and DNA extraction was performed to evaluate genetic mutations and nucleotide and amino acid variations. There was a statistically significant correlation between the extent of RORA and patient age, best-corrected visual acuity, ellipsoid zone extension, and disease severity in both eyes (each, P < 0.05). In contrast, RORA did not correlate with either the visual field or the ERG amplitude. Cumulative score and grade severity were both significantly correlated with superficial and deep capillary plexus density (both, P < 0.001) in both eyes. Evaluating RORA, we found genes with an overall less severe phenotype, such as EYS, PCDH15, and PRPF31, and those with a worse phenotype, such as RPGR. The correlation of RORA with structural, functional, and genetic assessment in RP disease leads us to consider RORA as a potential biomarker for prediction of disease stage. Multicenter studies are needed to confirm our findings. The morphofunctional and genetic correlations suggest a role for RORA in RP diagnosis and follow-up.

A light-fueled self-rolling unicycle with a liquid crystal elastomer rod engine

Active materials hold substantial potential for self-sustaining motion, however, the dependency on movable light or extensive area illumination in current structures often restricts the design and practical deployment of such active machines. In this study, we report a novel zero-energy-mode, self-rolling unicycle equipped with a liquid crystal elastomer rod engine, which fueled by a fixed, small-area light source. By employing an elaborate dynamic model for liquid crystal elastomer, we derive the lateral curvature of the liquid crystal elastomer rod and the driving moment necessary for the unicycle's self-rolling. The study results demonstrate that the self-rolling of the unicycle is driven by a moment induced by the shift in the center of gravity of the curved liquid crystal elastomer rod. Our numerical simulations indicate the presence of a supercritical Hopf bifurcation point delineating the transition between the self-rolling mode and the static mode within the unicycle system. Additionally, the rolling velocity of the unicycle relies on a handful of key system parameters, notably including light intensity, light penetration depth, length of the liquid crystal elastomer rod, rolling friction coefficient, total mass of the unicycle, and wheel radius of the unicycle. The experimental validation of a self-rolling unicycle with zero-energy-mode has been conducted. The self-rolling unicycle constructed in this paper has excellent characteristics of simple structure, zero-energy-mode, horizontal constant light source, and small area light source, providing valuable insights for the utilization of photoresponsive liquid crystal elastomer rods in soft robotics, medical devices, energy harvesting systems, and actuators.

Effects of artificial light on foraging behavior of the Pacific Kangaroo Rat (Dipodomys agilis)

Abstract Artificial light at night is increasingly recognized as a cause of habitat degradation, and as a conservation threat to wildlife species. We studied the behavioral response of Pacific kangaroo rats (Dipodomys agilis) to natural and artificial light in coastal sage scrub in southern California, United States. We used digital trail cameras to monitor visits to seed trays in shrub and open, intershrub microhabitats. Under natural-light conditions, kangaroo rats were more active on full- than new-moon nights, and concentrated foraging beneath shrubs. Surprisingly, kangaroo rats frequently interacted with other rodents in seed trays. Near to an artificial light source, kangaroo rats removed fewer seeds, had fewer foraging bouts, and spent less time in trays—especially in brightly lit open microhabitats—compared to distances farther from the light. Differences between the first and second nights of trials during both experiments suggested that kangaroo rats learned locations of resource-rich seed trays and modified their behavior accordingly. Our results are similar to recent studies showing that artificial light depresses foraging activity of rodents in the areas of highest illumination, and adds to evidence of the need to mitigate impacts of urban lighting in fragments of coastal sage scrub, especially along the urban–wildland interface.

Wide Dynamic Range, High Uniformity Spectral Irradiance Source for Calibration of Scientific-Grade, Large-Size Space Detectors

In order to meet the high uniformity calibration requirements for scientific-grade, large-size space detectors used in the CHES Extrasolar Planet Exploration Mission, this paper presents the design of a wide dynamic range, high uniformity spectral irradiance source (WHUIS). Utilizing a cascade integrating sphere design, and optimizing the overlapping area radiant flux adjustment structure and illumination light path, we achieve a wide dynamic range and high uniformity irradiance output. We established an irradiance transmission model based on the new assumption and analyzed the influence of factors such as illumination distance, stray light, and non-uniform radiance on the uniformity of irradiance output. The model is then validated by building experimental equipment. The findings show that in a circular area of 40 mm, the irradiance uniformity of our light source system exceeds 99.9%, and constant color temperature is adjustable within six orders of magnitude, consistent with the uniformity level predicted by the model.

Investigation on a novel hybrid system based on radiative sky cooling and split thermoelectric cooler driven by photovoltaic cell

This paper develops a novel cooling and heating system by integrating a novel split thermoelectric cooler (STEC) with photovoltaic power generation and radiative sky cooling. The system uses photovoltaic driven STEC modules to generate cooling and heating combined with radiative sky cooling to improve cooling capacity. By harnessing the distinctive characteristics of photovoltaic technology and radiative sky cooling, the new system is capable of operating continuously for 24 h without requiring any additional energy input. The system mathematical model is established, and the effects of STEC module number, solar illumination intensity, area ratio and ambient temperature on the performance are studied. Results demonstrate that the cooling efficiency of the system is 3.02 and the heating efficiency is 1.86 when the number of STEC modules is 3. In a year, the monthly average heat production of the system fluctuates due to changes in the solar illumination intensity, while the fluctuation of cooling capacity is small. The system cold production is larger than heat production, which is more suitable for application in the area with high demand for year-round refrigeration. The new system has good energy and economic performance with payback time being shorter than that of the photovoltaic-air conditioning system.

Battery-free optoelectronic patch for photodynamic and light therapies in treating bacteria-infected wounds

Light therapy is an effective approach for the treatment of a variety of challenging dermatological conditions. In contrast to existing methods involving high doses and large areas of illumination, alternative strategies based on wearable designs that utilize a low light dose over an extended period provide a precise and convenient treatment. In this study, we present a battery-free, skin-integrated optoelectronic patch that incorporates a coil-powered circuit, an array of microscale violet and red light emitting diodes (LEDs), and polymer microneedles (MNs) loaded with 5-aminolevulinic acid (5-ALA). These polymer MNs, based on the biodegradable composite materials of polyvinyl alcohol (PVA) and hyaluronic acid (HA), serve as light waveguides for optical access and a medium for drug release into deeper skin layers. Unlike conventional clinical photomedical appliances with a rigid and fixed light source, this flexible design allows for a conformable light source that can be applied directly to the skin. In animal models with bacterial-infected wounds, the experimental group with the combination treatment of metronomic photodynamic and light therapies reduced 2.48 log10 CFU mL−1 in bactericidal level compared to the control group, indicating an effective anti-infective response. Furthermore, post-treatment analysis revealed the activation of proregenerative genes in monocyte and macrophage cell populations, suggesting enhanced tissue regeneration, neovascularization, and dermal recovery. Overall, this optoelectronic patch design broadens the scope for targeting deep skin lesions, and provides an alternative with the functionality of standard clinical light therapy methods.

Ligand Homogenized Br-I Wide-Bandgap Perovskites for Efficient NiOx-Based Inverted Semitransparent and Tandem Solar Cells.

Phase heterogeneity of bromine-iodine (Br-I) mixed wide-bandgap (WBG) perovskites has detrimental effects on solar cell performance and stability. Here, we report a heterointerface anchoring strategy to homogenize the Br-I distribution and mitigate the segregation of Br-rich WBG-perovskite phases. We find that methoxy-substituted phenyl ethylammonium (x-MeOPEA+) ligands not only contribute to the crystal growth with vertical orientation but also promote halide homogenization and defect passivation near the buried perovskite/hole transport layer (HTL) interface as well as reduce trap-mediated recombination. Based on improvements in WBG-perovskite homogeneity and heterointerface contacts, NiOx-based opaque WBG-perovskite solar cells (WBG-PSCs) achieved impressive open-circuit voltage (Voc) and fill factor (FF) values of 1.22 V and 83%, respectively. Moreover, semitransparent WBG-PSCs exhibit a PCE of 18.5% (15.4% for the IZO front side) and a high FF of 80.7% (79.4% for the IZO front side) for a designated illumination area (da) of 0.12 cm2. Such a strategy further enables 24.3%-efficient two-terminal perovskite/silicon (double-polished) tandem solar cells (da of 1.159 cm2) with a high Voc of over 1.90 V. The tandem devices also show high operational stability over 1000 h during T90 lifetime measurements.

IDENTIFYING ILLUMINATION COVERAGE IN UP DILIMAN CAMPUS USING GIS

Abstract. The University of the Philippines Diliman faces challenges for pedestrians, particularly at night. Hence, this study proposed the creation of a detailed map using QGIS to showcase the illumination coverage of street lights around the UP Academic Oval. The project aims to establish a safer and more secure environment within the university community, ensuring optimal visibility and reducing the risk of accidents through a map that provides crucial insights into the spatial distribution of street lights, highlighting areas with sufficient lighting and areas in need of improvement. It considered significant factors that affect illumination quality across the campus such as terrain, lamp height, and bulb specifications. Based on the gathered data, increasing the lamp post height by a meter expands the illumination coverage around Roces Street and along paths towards University Avenue, but decreases light intensity. Changing the beam angles of the lamp posts from 112 to 140 degrees causes clustering of illumination areas along the left side of the Academic Oval, enhances those along Beta Way, and weakens light intensity of the lamp posts though not as much as in the first case. Lastly, increasing both the height of the lamp posts and their beam angles by a meter and at 140 degrees results in the significant increase of illumination coverage along the Academic Oval. However, increasing the heights of the posts may be costly. Therefore, to economically provide better coverage and maintain safety around the area, beam angles of the lamp posts should be increased to 140 degrees.

Abstract 5505: Automating a spatial profiling workflow to explore the effects of hypoxia in the tumor microenvironment in head and neck cancer

Abstract Head and neck cancer (HNC) is a heterogeneous group of malignancies that arise from the mucosal surfaces of the upper aerodigestive tract. The tumor microenvironment (TME) of HNC is characterized by the presence of immune cells, stromal cells, and extracellular matrix components. A key feature of the TME is hypoxia, which promotes tumor growth, invasion, and metastasis by altering the expression of genes involved in angiogenesis, cell survival, and metabolism. Understanding the complex interplay between hypoxia and immune infiltrates in the TME of HNC is crucial for the development of novel therapeutic strategies for the treatment of this disease. Whole transcriptome analysis by digital spatial profiling is an excellent method of probing the TME, but assessing large cohorts can be time consuming. Automating a profiling workflow to reduce hands-on time and region of interest (ROI) selection bias will enable exploration of large cohorts to identify mechanisms of action, potential drug targets, and biomarkers. We developed an optimized spatial multi-omic workflow to enable high-throughput spatial analysis on GeoMx® Digital Spatial Profiler (DSP) using the Whole Transcriptome Atlas (WTA) and immuno-fluorescent morphology markers: SYTO82 (nuclei), CAIX (hypoxia), pan-cytokeratin (epithelium), CD3 (T-cells). A.I.-based analysis (Oncotopix® Discovery) of serial section H&amp;E images and GeoMx IF images was developed to identify ROIs for GeoMx collection. Immune hot and cold selection used leukocyte density; tumor/stromal interface selection used epithelial areas. Areas of illumination (AOI) were chosen using concentric CAIX expression gradients. Integrated analysis of digital images using Oncotopix Discovery and the whole transcriptome was done to assess the above TME compartments. Automated ROI placement based on tumor/stroma, hypoxia and immune infiltration and AI/Deep Learning based AOI segmentation reduced AOI selection time and improved accuracy of tissue compartment enrichment, especially between samples and tissue types. Automated development of hypoxia gradient-based AOI enabled a selection strategy not possible in the standard DSP software. Cell phenotyping using IF morphology scan was used to supervise cell deconvolution. DSP results correlated well with patient outcomes. This work shows that ROI-based spatial analyses can be used to explore the effects of hypoxia levels on immune infiltration in HNC. Automated AI-based ROI selection provides a means of sampling relevant tumor subtypes based on hypoxia and immune infiltrate criteria in an unbiased, reproducible manner, and can provide a standardized, automated method for selecting ROIs and segmenting AOIs across a cohort of mixed tissue types and pathological subtype, improving throughput. Citation Format: David Mason, Kyla Teplitz, James Robert Mansfield, Kelly Hunter, Joana Campos, Jill Brooks. Automating a spatial profiling workflow to explore the effects of hypoxia in the tumor microenvironment in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5505.

Abstract 7471: Cancer-associated fibroblasts drive T cell infiltration and resistance to immunotherapy in non-small cell lung cancer with mature tertiary lymphoid structures

Abstract Background: The presence of mature tertiary lymphoid structures (mTLS) within the tumor microenvironment (TME) has been linked to the effectiveness of PD-L1 blockade in non-small cell lung cancer (NSCLC). However, only a subset of patients experiencing clinical benefit. Our study aims to delve into the determinants of immunotherapy response in mTLS-positive NSCLC. Methods: We included 77 TLS-positive NSCLC from the BIP study (NCT02534649). First, we employed the GeoMx whole-transcriptome atlas (WTA) assay to spatially profiled the expression of &amp;gt;18,000 protein-coding in patients exhibiting extreme responses (3 responders [R] and 3 non-responders [NR]). To target regions of interest (ROIs), we selected areas that encompassed TLS (CD3+/CD20+) as entire areas of illumination (AOIs). Additionally, we segmented areas outside TLS into ‘tumor’ (PanCK+/CD45−) vs ‘stroma’ (PanCK−/CD45+) AOIs. To validate our findings, we conducted multiplex immunofluorescence (mIF) and complemented our results with bulk gene expression analysis using the HTG whole human transcriptome panel. Results: Spatial transcriptomic analysis pinpointed significant differences in gene expression within the stromal compartment between R and NR. Notably, a subset of cancer-associated fibroblasts (CAFs) expressing both FAP and αSMA markers emerged as the most differentially expressed genes. Subsequently, we used FFPE tissue mIF to delineate the histological profile CAF subsets and the spatial distribution of T cells. Notably, the stromal density of FAP+αSMA+ CAFs and MYH11+αSMA+ CAFs were significantly higher in NR compared to R. Correspondingly, tumors enriched in FAP+αSMA+ CAFs and MYH11+αSMA+ CAFs exhibited significantly lower overall response rates (ORR) and progression-free survival (PFS) than those with a low abundance of CAFs. Interestingly, tumors with elevated FAP+αSMA+ CAFs and MYH11+αSMA+ CAFs were associated with a higher infiltration of CD8+ T cells. To delve deeper into the CD8+ T cell infiltrate, we conducted a comparative bulk transcriptomic analysis. Both FAP+αSMA+ CAFs High and MYH11+αSMA+ CAFs High demonstrated significant associations with regulatory T cells (Treg), exhaustion signatures, and inflammatory processes. To validate the CD8+ T cell phenotype, we performed complementary mIF. Consistently, the CD8+ T cell infiltrate in tumors featuring FAP+αSMA+ CAFs High and MYH11+αSMA+ CAFs High exhibited higher levels of exhaustion markers (PD1, LAG3, TIM3, TIGIT) and Treg infiltration, underscoring an immunosuppressive TME. Conclusions: FAP+αSMA+ CAFs and MYH11+αSMA+ CAFs play a pivotal role in driving T cell exhaustion and Treg cell infiltration, contributing to the resistance to immune checkpoint inhibition. Targeting these specific CAF subsets may hold significant promise in overcoming resistance in mature TLS-positive NSCLC. Citation Format: Florent Peyraud, Jean-Philippe Guegan, Lucile Vanhersecke, Christophe Rey, Oren Lara, Ophélie Odin, Emma Clot, Maxime Brunet, Thomas Grellety, Marie Del Castillo, Sylvestre Le Moulec, François Le Loarer, Alban Bessede, Antoine Italiano. Cancer-associated fibroblasts drive T cell infiltration and resistance to immunotherapy in non-small cell lung cancer with mature tertiary lymphoid structures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7471.

Abstract 5484: Spatial transcriptomic profiling reveals characteristic gene expression patterns of cancer-associated fibroblasts in lung adenocarcinoma with interstitial pneumonia

Abstract Background: Interstitial pneumonia (IP) is a risk factor for lung cancer (LC). LC, a significant contributor to mortality, shows improved prognosis with molecular targeted drugs. However, LC combined with IP (LC with IP) has a poor prognosis because of acute exacerbations. Therefore, developing effective drugs for LC with IP is necessary. Cancer-associated fibroblasts (CAFs), influencing cancer progression through interactions with the microenvironment are anticipated as a new therapeutic target. Therefore, we hypothesized that CAFs in LC with IP, having undergone repeated destruction and regeneration, exhibit distinct characteristics from those in LC without IP and exert varied influences on carcinogenesis and cancer progression. Methods: Six cases of lung adenocarcinoma, the predominant type of LC, were enrolled in this study. Spatial profiling was performed on FFPE specimens from three LC with IP and three LC without IP cases, using GeoMx whole-transcriptome atlas assay. Immunostaining for α-SMA, a major CAFs-marker, and pan-cytokeratin (CK), an epithelial marker, were employed to identify regions of interest (ROIs). In LC with IP, two ROIs were designated for cancerous and non-cancerous areas, respectively, whereas in LC without IP, two ROIs were selected for cancerous areas. Each ROI was segmented for epithelium and cancer (CK+/α-SMA -) and α-SMA-positive stroma (CK-/α-SMA +) areas of illumination. NGS data were analyzed using the edgeR to compare mRNA expressions in cancerous (LC-IP) and non-cancerous (NC) areas of LC with IP. Additionally, comparisons were made between LC-IP and cancerous areas of LC without IP (LC-nonIP) for mRNA expression. Results: Analysis of α-SMA-positive stroma revealed 86 differentially expressed genes (DEGs) in LC-IP vs. NC. Notably, COTL1 and NFKB2 increased, whereas TNC and MMP7 were decreased in LC-IP α-SMA-positive stroma. Pathway Enrichment analysis indicated activation of the response to cytokines. Between LC-IP and LC-nonIP, 151 DEGs were detected. CXCL8 and NFKB2 were elevated, whereas ACAN and ELN decreased in LC-IP α-SMA-positive stroma. KEGG pathway analysis demonstrated inactivated ECM-receptor interactions. Analysis of CK-positive regions showed 710 DEGs in LC-IP vs. NC, and KEGG pathway analysis indicated inactivated ECM-receptor interaction. In LC-IP vs. LC-nonIP, 321 DEGs were detected, with KEGG pathway analysis suggesting inactivation of ECM-receptor interaction and activation of a chemokine signaling pathway and cytokine-cytokine receptor interaction. Conclusion: These findings suggest that inflammatory factors may play a more critical role than extracellular matrix in the interaction between α-SMA-positive stroma and CK-positive cancer cells in LC with IP. Future plans include conducting in vitro experiments, as well as immunohistological studies. Citation Format: Chihiro Inoue, Yasuhiro Miki, Yayoi Aoyama, Saori Shibata, Yoshinori Okada, Takashi Suzuki. Spatial transcriptomic profiling reveals characteristic gene expression patterns of cancer-associated fibroblasts in lung adenocarcinoma with interstitial pneumonia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5484.

Abstract 6644: aPD1 treatment of urothelial cancers is synergistically enhanced by activating anti tumor immunity using vascular targeted photodynamic therapy

Abstract Background: Recurrence and progression rate following surgical treatment of locally advanced urothelial cancer is high, underscoring the unmet need to develop an effective, well tolerated treatment strategies, particularly for high grade upper tract urothelial cancer (HG-UTUC). The treatment success of low grade UTUC by vascular targeted photodynamic therapy (VTP) with WST11 (Padeliporfin) in phase I clinical trials led the FDA to approve Phase 3 trial in a fast track, orphan drug designation for low grade UTUC (ENLIGHT). Recently, treatment with immune checkpoint inhibitor (ICIs) of the PD1/PD-L1 axis has been approved for treatment of HG-UTUC. Yet, the failure rate of aPD1 therapy in HG-UTUC is high.We hypothesized that immune checkpoint inhibition needs to be complemented by the massive priming and accrual of newly activated anti-tumor immune cells through tumor immunogenic cell death. Early evidence indicated that WST11 VTP promotes anti-tumor immunity suggesting that VTP/aPD1 combinations may significantly improve the treatment success of HG-UTUC. Methods: Mice bearing s.c. MB49-Luc, were subjected to WST11 VTP at 14d post implantation at suboptimal dose of drug or partial area of illumination. 4 or 5 doses of aPD1 were intraperitonealy administrated every 3 days starting at 1d post VTP (aPD1+1), or every 3 days till 10 days post-treatment starting at 2 days before VTP (aPD1-2). Tumor progression was followed up to 90 days post treatment using IVIS. Hematoxylin-eosin staining, and multiplex immunohistochemistry (mIHC) were performed on controls and treated animals. Results: WST11 VTP with suboptimal drug dose, aPD1+1, and aPD1-2 resulted in 17%, 23% and 43% cure at day 90 post VTP. VTP at suboptimal drug dose combined with aPD1+1 or aPD1-2, resulted in 50% and 77% cure rate at 90 days, respectively. VTP with optimal drug dose (5mg/kg) but partial illumination resulted in 20% cure rate while combining this treatment modality with aPD1-2 resulted in 90% animal cure rate at day 90.At 24h post VTP mIHC showed a 2-3 fold increase of cytotoxic T cells, dendritic and NK cells, and a ~4 folds overexpression of PD1 and PD-L1 in the treated tumor tissue. At 2 days post aPD1-2 initiation, PD1 and PD-L1 apparent expression dropped to 0 and 2 folds higher than control, respectively. Following the combined VTP and aPD1-2 treatment, both PD1 and PDL-1 contents dropped down to zero and the CD8 content reached 3 folds enhancement compared to control. Conclusions: These observations indicate that elevating the content of anti-tumor immune cells in the tumor microenvironment by VTP in combination with ICI synergistically enhances the therapeutic effect providing a much higher complete cure compared with the individual therapies. The cure rate extent strongly depends on the synchronization of the two modalities providing guidelines for the clinical management of HG-UTUC treatment. Citation Format: Lilach Agemy, Keren Sasson, Tamar Yechezkel, Rachel Hamri, Raz Robas, David Kain, Avigdor Scherz. aPD1 treatment of urothelial cancers is synergistically enhanced by activating anti tumor immunity using vascular targeted photodynamic therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6644.

Liquid-metal-based three-dimensional microelectrode arrays integrated with implantable ultrathin retinal prosthesis for vision restoration

Electronic retinal prostheses for stimulating retinal neurons are promising for vision restoration. However, the rigid electrodes of conventional retinal implants can inflict damage on the soft retina tissue. They also have limited selectivity due to their poor proximity to target cells in the degenerative retina. Here we present a soft artificial retina (thickness, 10 μm) where flexible ultrathin photosensitive transistors are integrated with three-dimensional stimulation electrodes of eutectic gallium–indium alloy. Platinum nanoclusters locally coated only on the tip of these three-dimensional liquid-metal electrodes show advantages in reducing the impedance of the stimulation electrodes. These microelectrodes can enhance the proximity to the target retinal ganglion cells and provide effective charge injections (72.84 mC cm−2) to elicit neural responses in the retina. Their low Young’s modulus (234 kPa), owing to their liquid form, can minimize damage to the retina. Furthermore, we used an unsupervised machine learning approach to effectively identify the evoked spikes to grade neural activities within the retinal ganglion cells. Results from in vivo experiments on a retinal degeneration mouse model reveal that the spatiotemporal distribution of neural responses on their retina can be mapped under selective localized illumination areas of light, suggesting the restoration of their vision.