Photothermal therapy (PTT) stimulated by near-infrared-II (NIR-II) laser is an emerging tumor treatment technique owing to deeper tissue penetration and less damage to surrounding normal tissue. Fullerene C60 has good biocompatibility and demonstrates potential applications in photodynamic therapy, but individual C60 molecule has a wide optical bandgap and thus cannot absorb the NIR-II light, hindering its application in PTT. Herein, we report a bandgap engineering strategy by covalently bonding C60 molecules to form two-dimensional C60 network (2D-C60), fulfilling the first applications of unmodified fullerene in PTT. We synthesize two types of 2D-C60 based on different bonding patterns, namely hexagonal phase (HP-2D-C60) and tetragonal phase (TP-2D-C60) nanosheets, and carry out comparative studies on their optical properties, NIR-II PTT efficacies and electronic band structures. TP-2D-C60 exhibits narrower optical bandgap than HP-2D-C60, resulting in obvious NIR-II absorption and consequently functions as a novel PTA of NIR-II PTT. Besides, the indirect bandgap nature TP-2D-C60 introduces phonon interactions during electron transition and relaxation, facilitating heat generation. Under 1064 nm NIR-II laser irradiation, in vitro and in vivo antitumor studies reveal that TP-2D-C60 exhibits significant antitumor effects with a high photothermal conversion efficiency of 43.02 %, which is among the highest values obtained for carbon nanomaterials.

Triple-Negative Breast Cancer (TNBC) remains difficult to treat due to poor drug retention and metabolic plasticity that enable rapid adaptation to therapy. Here, we report a chondroitin sulfate-modified lipid nano-particle platform (DMAA LNPs) that enhances the intracellular performance of mitoxantrone-based combination therapy by leveraging coordinated CD44 engagement and Golgi-associated drug retention. This design leads to markedly increased MTO accumulation in TNBC cells and induces concurrent DNA damage, oxidative stress, and metabolic pressure. DMAA LNPs exhibited superior cellular uptake in 2D and 3D TNBC models and disrupted nutrient acquisition pathways, sensitizing tumor cells to chemotherapy and light-activated cytotoxicity. In vivo, DMAA LNPs achieved substantially higher tumor suppression compared with free mitoxantrone and single-agent controls, without causing significant systemic toxicity. These results demonstrate that directing drug payloads toward intracellular compartments critical for metabolic control represents an effective strategy to potentiate existing chemotherapeutics. The proposed platform provides a modular route to enhance subcellular drug action and may support more adaptable combination therapies for aggressive breast cancers.

Drug resistance in solid tumors has emerged as a critical challenge, with limited effective therapeutic options available. In this study, we find that chemotherapy induces an increased tumor neoantigens burden (TNB) in breast cancer patients and both non-resistant and chemo-resistant triple-negative breast cancer 4T1 tumor-bearing mice. Consistently, proteomic analysis reveals that tumor antigens derived from in vitro chemotherapy-treated paclitaxel (PTX)-resistant 4T1 cells (chemo-rAg) are enriched in damage-associated molecular patterns and neoantigens, highlighting their potential to elicit antitumor immunity against chemo-resistant tumors. Based on these findings, we utilize the feature of PTX resistance and develop a nanovaccine incorporating chemo-rAg and a prodrug of a toll-like receptor 7 (TLR7) agonist. In preclinical mouse models, the nanovaccine effectively suppresses PTX-resistant 4T1 tumor growth, and it also reverses the innate resistance of immune checkpoint inhibitors. Notably, the therapeutic benefit of the nanovaccine is augmented by chemotherapy, which facilitates in situ release of tumor antigens. These results suggest that a chemo-rAg-based nanovaccine represents a promising strategy based on the 'like cures like' principle to overcome drug resistance by utilizing the characteristic of the drug resistance itself.

Brain tumor is a common neurological surgical disease, where surgical resection is the primary treatment method. Neurosurgeons need to accurately determine the location of the tumor during tumor resection surgery, but existing clinical tumor identification technologies face numerous challenges, such as high equipment costs, long processing times, a certain degree of invasiveness, and insufficient image clarity. In this work, we propose a hyperspectral image detection algorithm based on the fusion of multiple features to maximize the determination of tumor boundaries. The algorithm establishes the machine learning models of Support Vector Machine (SVM) and Random Forest (RF) by integrating data features from optimal wavelengths, spectral indices, and textural features. Experimental results show that on different datasets, the classification accuracy of the three-feature fusion model is significantly higher than that of models using only two features or a single feature. Hyperspectral tumor image recognition can effectively help distinguish the tumors from the surrounding tissue, thereby enhancing the safety and thoroughness of tumor surgery.

Clinically inspired combination therapy has become an important strategy for improving cancer treatment by integrating direct tumor cytotoxicity with immune regulation. However, conventional co-administration of multiple chemotherapeutic and immunomodulatory agents often suffers from pharmacokinetic mismatch, insufficient tumor accumulation, systemic toxicity, and limited durable antitumor immunity. Herein, we developed a triple-drug chemo-immunotherapeutic nanoformulation, DSPE-PEG-CS@MTO@CTX@JQ1, by employing a previously validated DSPE-PEG-chondroitin sulfate dual-targeting nanoliposomal platform to co-deliver mitoxantrone (MTO), cyclophosphamide (CTX), and the BRD4 inhibitor JQ1. This strategy was designed to translate the therapeutic logic of clinical combination chemotherapy into a synchronized nanodelivery system capable of coordinating tumor killing, immune activation, and immune escape suppression. Mechanistically, MTO served as an immunogenic cell death inducer to promote calreticulin exposure, HMGB1 release, and tumor antigen presentation; CTX was introduced to attenuate immunosuppressive regulation, particularly by reducing regulatory T-cell-associated inhibition; and JQ1 suppressed BRD4-dependent PD-L1 transcription to limit adaptive immune escape. The DSPE-PEG-CS liposomal shell functioned as a validated delivery vehicle to improve circulation stability, reduce premature drug leakage, and enhance CD44-mediated tumor targeting. The resulting nanoformulation exhibited favorable particle size, morphology, and drug-loading performance, while effectively promoting dendritic cell maturation, remodeling tumor immune microenvironment, and strengthening antitumor immune responses. By integrating clinically inspired triple-drug chemotherapy with immunogenic cell death induction, immunosuppression relief, and PD-L1 transcriptional suppression, this work provides a rational nanomedicine strategy for converting chemotherapy-induced tumor damage into sustained antitumor immune responses.

Hypertrophied adenoids in children can impair breathing and lead to obstructive sleep apnea (OSA), often accompanied by abnormal growth and weakened stamina and immunity. However, the cause of the pathological transformation in these originally immune-enhancing lymphoid tissues remains unclear. Our study provides the first single cell transcriptomic and immune repertoire atlas of adenoids from normal snoring to mild, moderate, and severe OSA, and identified markedly asynchronous functional modules, transcriptional regulatory networks and intercellular communications during the progression of OSA. Children with severe OSA exhibited exhibit active Hippo, Notch, and Wnt signaling, alongside significant downregulation of energy synthesis. Analysis revealed compromised T-cell and B-cell immunity, as well as reduced antigen processing by innate immune cells, coupled with diminished cell-cell communication in severe OSA group. T-cell receptor and B-cell receptor sequencing results also support more infection imprints and abnormal germinal centers and antibody class switching. Mechanistically, HIF1A-mediated hypoxic signaling likely drives the downregulation of key immune components (including HLA and interferon molecules), positioning it as a promising therapeutic target for OSA.

Magnetic Particle Imaging (MPI) is a promising imaging modality that tracks magnetic nanoparticles (MNPs) to generate real-time, high-resolution images. However, achieving an optimal balance between strong signal strength and sharp image clarity remains challenging. Higher drive field frequencies improve the signal-to-noise ratio (SNR), but also risk image blurring due to nanoparticle relaxation effects. To address this, we developed an end-to-end MPI simulation framework that models MNPs behavior, magnetic field dynamics, signal acquisition, and image reconstruction across a wide frequency range (20-85 kHz). Central to this framework is Cross-Axis Harmonic Analysis (CAHA)-a novel, frequency-domain signal processing technique that adaptively extracts high-SNR harmonics from the x, y, and z directions for improved signal reconstruction. Using a simulated 3D vascular phantom, CAHA significantly enhanced image quality, achieving sub-millimeter resolution (0.8 mm FWHM at 85 kHz), strong noise suppression (nRMSE as low as 0.01), and structural fidelity (SSIM up to 0.94 at 55 kHz). The peak SNR reached 29.7 dB at 85 kHz. The signal processed with CAHA was also tested with other reconstruction methods; when combined with total variation regularization, CAHA achieved a pSNR of 37.91 dB. Evaluation on the Open MPI dataset further demonstrated up to 20 % resolution improvement, confirming CAHA's robustness on real-world data. Although minor blurring was observed at the highest frequency due to relaxation, CAHA consistently maintained image clarity. By leveraging directional harmonic content rather than the full signal, CAHA sets a new benchmark for sharper, faster, and more robust MPI imaging.

Fear of progression (FoP) is a prevalent psychological response to the real threats associated with cancer diagnosis, treatment, and disease trajectory, and it represents one of the most prominent sources of distress symptoms among patients with breast cancer. Persistently elevated FoP may not only negatively impact treatment outcomes but also contribute to excessive healthcare utilization and reduced quality of life. This study aimed to construct and validate a predictive model for FoP in postoperative breast cancer patients based on the Health Ecology Model. This multi-center cross-sectional study enrolled 347 postoperative breast cancer patients from three tertiary Grade-A general hospitals in Anhui Province, China, between March 25, 2024, and June 25, 2024. Univariable analysis and multivariable logistic regression were employed to identify independent predictors of FoP. A nomogram was then constructed based on these predictors and internally validated. Model performance was assessed in terms of discrimination, calibration, and clinical usefulness using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA), respectively. The prevalence of high FoP was 52.74

Taxane-based chemotherapy is a main treatment modality for ovarian cancer and other solid tumors, but chemoresistance limits the clinical efficacy. Studies have shown tumor interaction with macrophages in the tumor microenvironment (TME) plays a significant role in taxane resistance, yet the underlying molecular mechanisms are poorly understood. In this study, we employed translatome profiling of paclitaxel-treated cancer cells, live-cell imaging analysis, gene knockdown/knockout, and in vitro cancer-macrophage coculture assays to unravel a novel chemoresistance mechanism mediated by tumor-macrophage interaction via the NOTCH2-JAG1 axis. The in vitro data were further validated by multiple xenograft, syngeneic and patient-derived xenograft mouse tumor models of ovarian cancer as well as ovarian cancer patient samples. We found paclitaxel selectively induced translational upregulation of NOTCH2 via cytoplasmic polyadenylation, and this NOTCH2 upregulation persisted after mitotic exit. Subsequent NOTCH2 activation by JAG1 expressed mainly on the neighboring macrophages promoted tumor cell survival and simulated cytokine release, such as CSF1 and IL-1β, that recruited JAG1-expressing macrophages, thus forming a positive feedback loop that further enhanced the pro-tumor NOTCH2 activity. Genetic depletion or pharmacological inhibition of NOTCH2 with the γ-secretase inhibitor attenuated macrophage infiltration and sensitized tumor response to paclitaxel in multiple preclinical models of ovarian cancer. Moreover, single-cell RNA sequencing analysis identified a JAG1-high macrophage subset that was enriched by paclitaxel treatment and attenuated by NOTCH inhibition. Clinically, high NOTCH2 expression in ovarian tumors was associated with recurrence and shorter progression-free survival of ovarian cancer patients. Paclitaxel-induced translational upregulation of NOTCH2 enables immediate juxtacrine activation by JAG1-positive macrophages, coupling tumor cell survival with immune remodeling in the tumor microenvironment to drive chemoresistance. Our results suggest NOTCH2 is a viable biomarker for paclitaxel resistance and that combining NOTCH2 inhibitor with taxane is an effective therapeutic strategy to selectively disrupt tumor-macrophage interaction and overcome macrophage-mediated taxane resistance in NOTCH2-positive tumors.

BACKGROUND:Magnetic particle imaging (MPI) is an emerging functional imaging modality that enables high-resolution (HR) visualization of superparamagnetic iron oxide nanoparticles (SPIONs). It offers significant advantages, including high penetration capability, absence of ionizing radiation, high contrast, and exceptional temporal resolution and sensitivity, making it highly promising for a broad spectrum of biomedical and clinical applications. PURPOSE:Although MPI holds great promise, fundamental spatial resolution is inherently constrained by the gradient field strength and the saturation magnetization physics of the SPIONs. To address the image blurring characterized by the system's point spread function (PSF) and the dependency on high-gradient fields for HR imaging, this study aims to develop a robust deep learning framework to reduce reliance on high gradient hardware. We aim to achieve high-fidelity resolution enhancement computationally, recovering fine structural details from low-resolution inputs, thereby bypassing the need for costly hardware upgrades. METHODS:We propose a Multiscale Frequency Attention Transformer (MFAT) model, which integrates a frequency-domain discriminative feedforward network (DFFN) with a multiscale attention block (MAB) to form an end-to-end framework for recovering HR MPI images from low-resolution reconstructions. The MFAT architecture combines multiscale feature aggregation with a novel frequency attention mechanism, allowing it to capture both global context and fine local details across multiple scales while enhancing fidelity and sharpness in the frequency domain. RESULTS:Extensive evaluations using both simulated and real-world MPI data demonstrate that the proposed MFAT model outperforms existing state-of-the-art deep learning methods, achieving an improvement of 7.51% in peak signal-to-noise ratio (PSNR) in the MNIST dataset, corresponding to a gain of 2.48 dB over the second strongest baseline. Furthermore, in terms of spatial resolution, MFAT significantly reduced the full width at half maximum (FWHM) by 17.86% on the complex FIVES vascular structures compared to the second-performing baseline, verifying its superior capability in recovering high-frequency details. CONCLUSIONS:Thus, MFAT provides an effective solution for enhancing spatial resolution in MPI image reconstruction and significantly improves image quality. This advancement holds strong potential to facilitate the translation of MPI technology into more refined clinical applications.

Abstract Purpose: This randomized, double-blind phase 3 equivalence study aimed to evaluate the similarity of neoadjuvant pertuzumab biosimilar HLX11 versus reference pertuzumab plus trastuzumab and docetaxel for human epidermal growth factor receptor 2-positive, hormone receptor-negative early-stage or locally advanced breast cancer (BC). Patients and Methods: Eligible patients were randomly assigned (1:1) to receive 4 cycles of neoadjuvant HLX11 (HLX11 arm) or European Union-sourced pertuzumab, plus trastuzumab and docetaxel (EU-pertuzumab arm). Patients in the respective arms received adjuvant HLX11 plus trastuzumab or were re-randomized (1:1) to receive HLX11 or EU-pertuzumab plus trastuzumab. The primary endpoint was blinded independent central review (BICR)-assessed total pathological complete response (tpCR) rate. Results: In total, 908 patients were randomized to the HLX11 (n = 454) or EU-pertuzumab arm (n = 454); 192 patients in HLX11 arm received adjuvant HLX11; 200 patients in EU-pertuzumab arm were re-randomized to receive adjuvant HLX11 (n = 100) or EU-pertuzumab (n = 100). BICR-assessed tpCR rate (95% confidence interval [CI]) was 46.3% (41.6%–51.0%) and 45.8% (41.2%–50.5%), respectively. The equivalence criteria were met, with relative risk of tpCR (90% CI) of 1.01 (0.90–1.14) and relative difference (95% CI) of 0.47% (−5.99%–6.92%). No clinically meaningful differences were observed in other efficacy endpoints, safety, pharmacokinetics (PK), or immunogenicity. In the adjuvant phase, switching from EU-pertuzumab to HLX11 led to no notable differences in safety, PK, or immunogenicity. Conclusions: Compared with EU-pertuzumab, neoadjuvant HLX11 demonstrated a similar tpCR rate and no clinically meaningful differences in other efficacy endpoints, safety, PK, or immunogenicity in BC.

This study presents a hybrid deep learning framework, the Vision Transformer with Residual Feature Network (VRF-Net), for recovering high-resolution system matrices in Magnetic Particle Imaging (MPI). MPI resolution often suffers from downsampling and coil sensitivity variations. VRF-Net addresses these challenges by combining transformer-based global attention with residual convolutional refinement, enabling recovery of both large-scale structures and fine details. To reflect realistic MPI conditions, the system matrix is degraded using a dual-stage downsampling strategy. Training employed paired-image super-resolution on the public Open MPI dataset and a simulated dataset incorporating variable coil sensitivity profiles. For system matrix recovery on the Open MPI dataset, VRF-Net achieved nRMSE = 0.403, pSNR = 39.08 dB, and SSIM = 0.835 at 2x scaling, and maintained strong performance even at challenging scale 8x (pSNR = 31.06 dB, SSIM = 0.717). For the simulated dataset, VRF-Net achieved nRMSE = 4.44, pSNR = 28.52 dB, and SSIM = 0.771 at 2x scaling, with stable performance at higher scales. On average, it reduced nRMSE by 88.2%, increased pSNR by 44.7%, and improved SSIM by 34.3% over interpolation and CNN-based methods. In image reconstruction of Open MPI phantoms, VRF-Net further reduced reconstruction error to nRMSE = 1.79 at 2x scaling, while preserving structural fidelity (pSNR = 41.58 dB, SSIM = 0.960), outperforming existing methods. These findings demonstrate that VRF-Net enables sharper, artifact-free system matrix recovery and robust image reconstruction across multiple scales, offering a promising direction for future in vivo applications.

Peripheral nerves contribute to tumor progression, but the mechanisms by which neural signals regulate cancer cell plasticity and immune resistance remain unclear. Using a paired murine model of intraneural and nonintraneural tumor growth with single-cell RNA sequencing, we identified a nerve-associated cancer cell state marked by increased expression of secretory leukocyte protease inhibitor (SLPI). SLPI was elevated in intraneural tumors and in human tumors with perineural invasion. Sensory neuron-derived substance P (SP) induced SLPI secretion through tumor cell TACR1, whereas sensory denervation or TACR1 blockade reduced SLPI production. SLPIhigh cancer cells were enriched for WNT/β-catenin and stemness programs. Consistent with this, SLPI increased β-catenin and c-MYC expression, expanded ALDH+ stem-like cells, and enhanced mammosphere formation, whereas Slpi deletion reduced stemness and impaired tumor growth in vivo. SLPI also limited immune-mediated tumor cell killing. Proteomic and biochemical analyses identified granzyme B as a direct SLPI-binding partner, and SLPI inhibited granzyme B-dependent cleavage of caspase-3 and gasdermin E, thereby reducing cytotoxic lymphocyte-induced cell death. In immunocompetent mouse models, pharmacologic inhibition of the upstream SP-TACR1 pathway with aprepitant synergized with anti-PD-1 therapy. In clinical datasets, high SLPI expression was associated with residual disease after immunotherapy, poor response, and adverse outcome. Together, these findings identify the SP-TACR1-SLPI axis as a neural pathway linking cancer stemness to immune escape and nominate this pathway as a target for combination immunotherapy.

580 Background: Breast-conserving surgery (BCS) is the standard treatment for early-stage breast cancer and is increasingly preferred by younger patients. The key challenge in BCS is ensuring complete tumor removal while preserving healthy breast tissue. Surgical margin assessment plays a crucial role in reducing the risk of local recurrence. Traditional intraoperative frozen sections (FS) are time-consuming, limit sampling, and may cause tissue damage. This study evaluates the performance of EndoScell, a handheld fluorescence microscopy system, as a rapid and efficient alternative for intraoperative margin assessment. Methods: EndoScell provides real-time, high-resolution imaging of tissue margins during surgery. This system rapidly stains and scans tissue, allowing for micron-level visualization of cellular features. In this study, EndoScell was used to scan marked surfaces of breast tissue during surgery. The surgeon performed an initial assessment, while images/videos were recorded. Specimens were then sent for intraoperative FS analysis for comparison. If FS identified positive margins, the area was re-excised by 3–5 mm, and the process was repeated. Routine paraffin pathology served as the gold standard, with blinded side-by-side reading of ES images to evaluate consistency. Results: As of December 31, 2025, 300 patients undergoing BCS were included. EndoScell demonstrated high diagnostic accuracy with a sensitivity of 96.4%, specificity of 95.1%, and AUC of 0.953, showing strong agreement with paraffin pathology. Notably, the time required for EndoScell imaging was significantly shorter than FS, with an average of 3.14 ± 1.48 minutes compared to 37.50 ± 13.34 minutes for FS (P<0.001), leading to substantial improvements in surgical efficiency. Conclusions: This study confirms the feasibility and non-inferiority of EndoScell for intraoperative margin assessment in breast-conserving surgery. The system enables real-time decision-making, reducing secondary surgeries, improving outcomes, and enhancing surgical safety. Its significant clinical and social value supports further development and implementation. Key metrics related to diagnostic accuracy and time efficiency between EndoScell and traditional frozen section methods. Metric EndoScell (ES) Frozen Section (FS) Positive Margin 54 56 Negative Margin 246 244 Sensitivity 0.964 1.000 Specificity 0.951 1.000 AUC 0.953 (95% CI: 0.912–1.003) 1.000 Imaging Time (min) 3.14 ± 1.48 37.50 ± 13.34 p-value <0.001 N/A Cohen's d -3.64 N/A

Magnetic particle imaging (MPI) is a promising tracer-based imaging modality for biomedical applications. While two-dimensional (2D) MPI provides limited planar information, high-quality three-dimensional (3D) imaging delivers the complete volumetric spatial distribution of nanoparticles, which is crucial for precise lesion localization and comprehensive functional analysis. However, the development of 3D MPI is challenged by complex system architectures and the particularly time-consuming measurement of the 3D system matrix. In this paper, we present a 3D mixing-domain MPI method, which combines the frequency domain information in x direction and spatial domain information in y and z directions. A key contribution is a novel and fast measurement strategy based on symmetric transformation for the 3D system matrix. By exploiting the symmetry of the selection field, this symmetric transformation strategy significantly reduces measurement time compared to conventional approaches. Furthermore, a 3D mixing-domain MPI scanner with a bore size of 30 mm is designed and built, which can generate a drive field in x-direction and shift field in the y-direction and z-direction, to enable full 3D imaging. Phantom experiments demonstrate that the proposed approach can provide 3D MPI images with good quality and improve the spatial resolution compared with the slice-based imaging method.

The mechanisms by which circRNAs regulate estrogen receptor (ER)-positive breast progression and therapeutic resistance remain poorly defined. By screening circRNAs involved in ER signaling, circESR1 was identified as a novel circRNA exhibiting high specificity of expression in ER+ breast cancer. CircESR1 interacted with HNRNPAB, which was transcriptionally activated by ER/SP1 signaling. HNRNPAB promoted the back-splicing and expression of circESR1 by binding to the Alu elements of cognate pre-mRNA; and circESR1 transcripts increased the stability and expression of HNRNPAB, ensuring an efficient positive feedback loop as reflected in antiestrogen-resistant breast cancer cells. Furthermore, HNRNPAB interacted and stabilized CDK1 and CDK6 mRNA, which was facilitated by its asymmetrical binding of circESR1, to promote cell cycle progression. Patients whose cancer exhibited high levels of circESR1 and/or HNRNPAB exhibited advanced prognostic stage and poor survival. Combined use of circESR1 ASO and CDK4/6 inhibitors were shown to be an effective therapeutic approach overcoming antiestrogen resistance in breast cancer xenograft models. Hence, these findings elucidated a novel signaling complex centered around circESR1 and HNRNPAB in ER+ breast cancer, and suggested that circESR1 might represent a potential therapeutic target for this disease.

IMPORTANCE:The combination of neoadjuvant taxanes with trastuzumab and pertuzumab remains the cornerstone treatment strategy in ERBB2-positive breast cancer. Anbenitamab (a ERBB2-biparatopic antibody that induces profound receptor clustering) and HB1801 (a solvent-free albumin-bound docetaxel), have shown promising antitumor activity and an acceptable safety profile in patients with breast cancer. OBJECTIVE:To evaluate whether neoadjuvant anbenitamab combined with HB1801 could improve efficacy without increasing toxic effects for patients with early ERBB2-positive breast cancer. DESIGN, SETTING, AND PARTICIPANTS:This multicenter, phase 3 registrational randomized clinical trial enrolled patients with stage II or III ERBB2-positive breast cancer from 61 hospitals in China between December 19, 2024, and August 29, 2025 (data cutoff: January 28, 2026). Data were analyzed from February 1 to March 20, 2026. INTERVENTIONS:Patients were randomly assigned (1:1) to receive 6 cycles of neoadjuvant anbenitamab plus HB1801, with or without carboplatin (investigational group), or trastuzumab, pertuzumab, and docetaxel, with or without carboplatin (control group). MAIN OUTCOMES AND MEASURES:The primary end point was total pathological complete response (tpCR) assessed by a blinded independent review committee. RESULTS:Among 521 included patients (median [IQR] age, 52.0 [23-79] years), 263 were randomized to the investigational group and 258 to the control group. The tpCR rate was significantly higher in the investigational group than the control group (164 patients [62.4%] vs 132 patients [51.2%]; absolute difference, 11.4 [95% CI, 3.2 to 19.6] percentage points; P = .004). Benefit was consistent across subgroups, including subgroups with hormone receptor-positive disease (77 patients [51.7%] vs 63 patients [44.4%]), hormone receptor-negative disease (87 patients [76.3%] vs 69 patients [59.5%]), early-stage disease (111 patients [63.8%] vs 87 patients [51.8%]), locally advanced disease (53 patients [59.6%] vs 45 patients [50.0%]), with carboplatin treatment (74 patients [66.7%] vs 61 patients [54.5%]), and without carboplatin treatment (90 patients [59.2%] vs 71 patients [48.6%]). Grade 3 or 4 treatment-related adverse events occurred in 77 patients (29.3%) in the investigational group and 73 patients (28.3%) of the control group. No treatment-related deaths occurred. CONCLUSIONS AND RELEVANCE:This randomized clinical trial found that neoadjuvant anbenitamab and HB1801 in patients with breast cancer significantly improved the tpCR rate compared with standard therapy with a highly manageable safety profile. This new combination may offer an improved treatment option, although long-term survival follow-up analyses are warranted. Trial Registration:ClinicalTrials.gov Identifier: NCT06747338.

Background: For early or locally advanced TNBC, preferred neoadjuvant strategies include a four-drug chemotherapy regimen containing anthracyclines, cyclophosphamide, taxanes, and platinum. Accumulating evidence suggests that blockade of the PD-1/PD-L1 pathway may enhance the efficacy of conventional neoadjuvant chemotherapy. Camrelizumab is an anti-PD-1 antibody that has demonstrated antitumor activity in advanced or metastatic TNBC. Herein, we conducted a double-blind, randomized phase 3 trial (NCT04613674) to evaluate the efficacy and safety of neoadjuvant camrelizumab plus chemo in early or locally advanced TNBC. Methods: Patients with previously untreated, invasive stage II (T2N0-1M0/T3N0M0) or III (T2N2-3M0/T3N1-3M0) TNBC were randomized (1:1) to receive neoadjuvant camrelizumab (200 mg, Q2W) or placebo plus chemo (nab-paclitaxel [100 mg/m2, D1, D8, D15, Q4W] + carboplatin [AUC 1.5, D1, D8, D15, Q4W] for 16 weeks, followed by dose-dense epirubicin [90 mg/m2, Q2W] + cyclophosphamide [500 mg/m2, Q2W] for 8 weeks). Randomization was stratified by tumor clinical stage (stage II vs III) and PD-L1 expression (combined positive score [CPS] <10 vs ≥10). After surgery, patients allocated to the camrelizumab group received camrelizumab (200 mg, Q2W) for up to a year (from first dose). The primary endpoint was pathological complete response (pCR; ypT0/is ypN0). Secondary endpoints included event-free survival (EFS), disease-free survival (DFS), distant disease-free survival (DDFS), and pre-surgery objective response rate (ORR; per RECIST v1.1). Results: As of data cutoff (Sep.30, 2023), 441 patients were randomized and treated (camrelizumab, n=222; placebo, n=219). Median follow-up was 14.4 mo. Overall, median age was 48.2 years; 35.8% of patients had stage III disease at baseline, and 70.5% presented with nodal involvement (N3 disease, 9.1%). pCR rate was 56.8% (95% CI 50.0-63.4) with camrelizumab + chemo and 44.7% (95% CI 38.0-51.6) with placebo + chemo (rate difference, 12.2% [95% CI 3.3 to 21.2]; 1-sided p=0.0038). The benefit in pCR with camrelizumab + chemo was observed regardless of PD-L1 expression, nodal status or disease stage at baseline. Specifically, among patients with poor prognostic factors, the pCR rate with camrelizumab + chemo vs placebo + chemo was 57.8% (89/154) vs 42.7% (67/157) for node-positive disease (rate difference, 15.1% [95% CI 4.1 to 26.1]), and 49.4% (39/79) vs 38.0% (30/79) for stage III disease (rate difference, 11.4% [95% CI -4.0 to 26.8]). Pre-surgery ORR reached 87.4% (95% CI 82.3 to 91.5) with camrelizumab + chemo and 82.6% (95% CI 77.0 to 87.4) with placebo + chemo. EFS (HR, 0.80 [95% CI 0.46-1.42]), DFS (HR 0.58 [95% CI 0.27 to 1.24]) and DDFS (HR 0.62 [95% CI 0.29-1.33]) were immature, with a trend favoring the camrelizumab + chemo group. Across stages, TRAEs of grade ≥3 occurred in 90.1% of patients in the camrelizumab + chemo group vs 82.6% in the placebo + chemo group; all events with incidence ≥10% were hematological toxicities. Conclusions: Addition of camrelizumab to platinum-containing intensive neoadjuvant chemotherapy significantly improved pCR rate in early or locally advanced TNBC, with a manageable safety profile. Early survival data also favored the camrelizumab + chemo group. Citation Format: Zhi-Ming Shao, Li Chen, Hui Li, Hao Zhang, Huawei Yang, Jun Qian, Zhihua Li, Yu Ren, Shu Wang, Peifen Fu, Hongjian Yang, Yunjiang Liu, Jing Sun, Jianyun Nie, Ruiwen Lei, Yongzhong Yao, Anqin Zhang, Shouman Wang, Xiaopeng Ma, Zhong Ouyang, Hongwei Yang, Song-Yang Wu, Shuo-Wen Cao, Kun Wang, Aimei Jiang, Quchang Ouyang, Da Pang, Limin Wei, Xiaoming Zha, Yu Shen, Xiangwen Qu, Fei Wu, Xiaoyu Zhu, Zhong-Hua Wang, Lei Fan & the CamRelief Study Group. Neoadjuvant camrelizumab plus chemotherapy (chemo) for early or locally advanced triple-negative breast cancer (TNBC): a randomized, double-blind, phase 3 trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr GS3-06.

Neoadjuvant chemotherapy (NAC) is a standard treatment for breast cancer (BC) to shrink tumors and facilitate surgery. However, the molecular underpinnings of response to NAC and prognosis have not been well characterized. We enrolled 73 stage II/III BC patients who received NAC followed by surgery. Tumor tissue samples were available from 36 patients at baseline and 38 at the time of surgery. Plasma circulating tumor DNA (ctDNA) was collected at three time points: before NAC (n = 63), during NAC (n = 42), and after NAC (n = 40). Comprehensive genomic, transcriptomic, and ctDNA analyses were performed to identify biomarkers associated with pathological complete response (pCR) and survival outcomes. Nine baseline mutations, including DNHD1 and PLEC, along with HIPPO pathway alterations, were associated with pCR. Responsive tumors exhibited immune activation and downregulated PI3K-Akt and AGE-RAGE pathways, while non-pCR tumors showed reduced cytokine and immune receptor activity. Undetectable ctDNA during and after NAC was predictive of treatment efficacy and correlated with improved survival. Baseline mutations in USH2A were associated with shorter disease-free survival (hazard ratio: 11.9; 95

Flexible pressure-temperature bifunctional sensor is an important component for realizing electronic skin, which plays an important role in human-computer interaction and health monitoring. However, complex environments require sensors with higher sensitivity, and the problem of mutual coupling between the signals of pressure-temperature bifunctional sensors remains to be solved. In this study, flexible pressure-temperature bifunctional sensors (FPTB-sensors) were proposed, which were based on ionic capacitors and temperature-sensitive resistors. Electrostatic spinning films with microcone structures were obtained by template-assisted electrostatic spinning and impregnation process, which enabled the FPTB-sensors to obtain high pressure sensitivities of 340. 02 kPa-1 (0-110 kPa) and 34.4 kPa-1 (110-300 kPa). By doping the thermoplastic polyurethanes/carbon nanotube material with ionic liquid, a temperature sensitivity of 0.0297 degrees C-1 was obtained with a detection range of up to 80 degrees C. In addition, the pressure signal was self-decoupled from the temperature signal due to the different sensing mechanisms for pressure or temperature. Finally, the FPTB-sensors were applied to a robotic electronic skin to enable the detection of different objects by grasping.