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Multi-omics and spatial transcriptomics reveal that S100A10 drives CD8+ T-cell exhaustion and immune evasion in hepatocellular carcinoma through cPLA2-5-LOX-mediated arachidonic acid metabolism and ferroptosis

βœ‡Omics in Hepatocellular
By: Jingxu Zhang Β· Ganggang Wang Β· Zhijie Zhou Β· Bingbing Pu Β· Xin Zhang Β· Xinyu Ji Β· Xiaoliang Wang

Int Immunopharmacol. 2026 Sep 13;189:117355. doi: 10.1016/j.intimp.2026.117355. Online ahead of print.

ABSTRACT

Immune evasion in hepatocellular carcinoma (HCC) represents a major biological barrier limiting the efficacy of immunotherapy, yet its molecular basis remains incompletely understood. Increasing evidence indicates that tumor metabolic reprogramming and ferroptosis-related signaling play critical roles in shaping an immunosuppressive tumor microenvironment (TME); however, the specific regulatory factors involved remain unclear. This study aims to systematically elucidate the functional role of S100 calcium-binding protein A10 (S100A10) in immune evasion in HCC, with a particular focus on the molecular mechanisms by which S100A10 regulates CD8+ T-cell exhaustion through arachidonic acid (AA) metabolism and ferroptosis, as well as its potential therapeutic implications. To this end, data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort are integrated to analyze the expression patterns of S100A10, its prognostic value, and its association with the immune microenvironment. S100A10 overexpression and knockout models are established in HCCLM3 and MHCC97L cell lines, and S100A10-mediated metabolic pathway reprogramming is characterized using transcriptomic profiling, untargeted metabolomics, and ferroptosis-related functional assays. In parallel, single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics are employed to delineate the cell-type specificity and spatial distribution of S100A10. Furthermore, human CD8+ T-cell co-culture systems and orthotopic mouse HCC models are used to evaluate the impact of S100A10 on immune function and responsiveness to anti-programmed cell death protein 1 (anti-PD-1) therapy. The results demonstrate that S100A10 is significantly upregulated in HCC and is closely associated with poor prognosis and an immunosuppressive state. Mechanistically, S100A10 activates cytosolic phospholipase A2-arachidonate 5-lipoxygenase (cPLA2-5-LOX)-mediated AA oxidative metabolism, leading to the accumulation of lipid peroxidation products and ferroptosis-associated signals, thereby driving CD8+ T-cell exhaustion and promoting immune evasion. Significantly, inhibition of S100A10 reshapes the tumor immune microenvironment (TIME) and enhances the therapeutic efficacy of anti-PD-1 treatment. Collectively, these findings identify S100A10 as a critical regulator of metabolic-immune coupling in HCC and provide a theoretical basis for combinatorial strategies targeting metabolism and immunotherapy.

PMID:42732672 | DOI:10.1016/j.intimp.2026.117355

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Multi-omics and spatial transcriptomics reveal that S100A10 drives CD8+ T-cell exhaustion and immune evasion in hepatocellular carcinoma through cPLA2-5-LOX-mediated arachidonic acid metabolism and ferroptosis

βœ‡(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Jingxu Zhang Β· Ganggang Wang Β· Zhijie Zhou Β· Bingbing Pu Β· Xin Zhang Β· Xinyu Ji Β· Xiaoliang Wang

Int Immunopharmacol. 2026 Sep 13;189:117355. doi: 10.1016/j.intimp.2026.117355. Online ahead of print.

ABSTRACT

Immune evasion in hepatocellular carcinoma (HCC) represents a major biological barrier limiting the efficacy of immunotherapy, yet its molecular basis remains incompletely understood. Increasing evidence indicates that tumor metabolic reprogramming and ferroptosis-related signaling play critical roles in shaping an immunosuppressive tumor microenvironment (TME); however, the specific regulatory factors involved remain unclear. This study aims to systematically elucidate the functional role of S100 calcium-binding protein A10 (S100A10) in immune evasion in HCC, with a particular focus on the molecular mechanisms by which S100A10 regulates CD8+ T-cell exhaustion through arachidonic acid (AA) metabolism and ferroptosis, as well as its potential therapeutic implications. To this end, data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort are integrated to analyze the expression patterns of S100A10, its prognostic value, and its association with the immune microenvironment. S100A10 overexpression and knockout models are established in HCCLM3 and MHCC97L cell lines, and S100A10-mediated metabolic pathway reprogramming is characterized using transcriptomic profiling, untargeted metabolomics, and ferroptosis-related functional assays. In parallel, single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics are employed to delineate the cell-type specificity and spatial distribution of S100A10. Furthermore, human CD8+ T-cell co-culture systems and orthotopic mouse HCC models are used to evaluate the impact of S100A10 on immune function and responsiveness to anti-programmed cell death protein 1 (anti-PD-1) therapy. The results demonstrate that S100A10 is significantly upregulated in HCC and is closely associated with poor prognosis and an immunosuppressive state. Mechanistically, S100A10 activates cytosolic phospholipase A2-arachidonate 5-lipoxygenase (cPLA2-5-LOX)-mediated AA oxidative metabolism, leading to the accumulation of lipid peroxidation products and ferroptosis-associated signals, thereby driving CD8+ T-cell exhaustion and promoting immune evasion. Significantly, inhibition of S100A10 reshapes the tumor immune microenvironment (TIME) and enhances the therapeutic efficacy of anti-PD-1 treatment. Collectively, these findings identify S100A10 as a critical regulator of metabolic-immune coupling in HCC and provide a theoretical basis for combinatorial strategies targeting metabolism and immunotherapy.

PMID:42732672 | DOI:10.1016/j.intimp.2026.117355

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POC1A promotes the proliferation, metastasis and stemness of bladder cancer by stabilizing BMI1 via USP7

βœ‡Oncogene - Issue - nature.com science feeds
By: Houyi Wei Β· Renran Bai Β· Jianmin Liu Β· Lei Lyu Β· Jingdong Yuan Β· Wan Xiang Β· Kaiyu Qian Β· Fangjin Chen Β· Lingao Ju Β· Yi Zhang Β· Yu Xiao Β· Gang Wang

Oncogene, Published online: 31 August 2026; doi:10.1038/s41388-026-03973-9

POC1A promotes the proliferation, metastasis and stemness of bladder cancer by stabilizing BMI1 via USP7
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Imaging interface-controlled bulk oxygen spillover

βœ‡Nature - Issue - nature.com science feeds
By: Weijue Wang Β· Hongbin Xu Β· Shuhui Liu Β· Xiaofeng Yang Β· Wei Liu Β· Yang-Gang Wang Β· Yanqiang Huang Β· Tao Zhang

Nature, Published online: 15 April 2026; doi:10.1038/s41586-026-10324-x

In situ microscopic single-particle imaging demonstrates the significance of rationally engineered metal–support interfaces for activating the oxygen in bulk catalyst, helping elucidate reaction pathways in catalytic conversions.
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InfiniteVL: Synergizing Linear and Sparse Attention for Highly-Efficient, Unlimited-Input Vision-Language Models

βœ‡cs.AI, q-bio.NC updates on arXiv.org
By: Hongyuan Tao Β· Bencheng Liao Β· Shaoyu Chen Β· Haoran Yin Β· Qian Zhang Β· Wenyu Liu Β· Xinggang Wang
arXiv:2512.08829v2 Announce Type: replace-cross Abstract: Vision-Language Models (VLMs) are increasingly tasked with ultra-long multimodal understanding. While linear architectures offer constant computation and memory footprints, they often struggle with high-frequency visual perception compared to standard Transformers. To bridge this gap, we introduce \textbf{InfiniteVL}. We first develop a hybrid base model called \textbf{InfiniteVL-Base} that interleaves a small fraction of Full Attention layers with Gated DeltaNet. Empowered by a tailored distillation and fine-tuning strategy, InfiniteVL-Base matches the fundamental multimodal performance of equivalent Transformers while achieving a \textbf{1.7$\times$} decoding speedup. However, the quadratic complexity of the retained Full Attention inevitably becomes an efficiency bottleneck when scaling to ultra long context. To break this barrier, we propose a novel Long-Sequence Architectural Fine-Tuning strategy that seamlessly transforms the dense attention into vision-specific sparse mechanisms. This yields two specialized variants: \textbf{InfiniteVL-Offline} for offline retrieval and \textbf{InfiniteVL-Online} for online streaming. By eliminating the computation explosion of global attention without sacrificing high-frequency visual recall, InfiniteVL-Offline achieves Transformer-level length generalization with a \textbf{5x} prefill acceleration at 256K context. Concurrently, InfiniteVL-Online delivers robust streaming perception with a constant memory footprint and a real-time throughput of \textbf{25} FPS. Code and models are available at https://github.com/hustvl/InfiniteVL.
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DiaBlo: Diagonal Blocks Are Sufficient For Finetuning

βœ‡cs.AI, q-bio.NC updates on arXiv.org
By: Selcuk Gurses Β· Aozhong Zhang Β· Yanxia Deng Β· Xun Dong Β· Xin Li Β· Naigang Wang Β· Penghang Yin Β· Zi Yang
arXiv:2506.03230v2 Announce Type: replace-cross Abstract: Fine-tuning is a critical step for adapting large language models (LLMs) to domain-specific downstream tasks. To mitigate the substantial computational and memory costs of full-model fine-tuning, Parameter-Efficient Fine-Tuning (PEFT) methods have been proposed to update only a small subset of model parameters. However, performance gaps between PEFT approaches and full-model fine-tuning still exist. In this work, we present DiaBlo, a simple yet effective PEFT approach that updates only the diagonal blocks of selected model weight matrices. Unlike Low-Rank Adaptation (LoRA) and its variants, DiaBlo eliminates the need for low-rank matrix products, thereby avoiding the reliance on auxiliary initialization schemes or customized optimization strategies to improve convergence. This design leads to stable and robust convergence while maintaining comparable memory efficiency and training speed to LoRA. Moreover, we provide theoretical guarantees showing that, under mild low-rank conditions, DiaBlo is more expressive than LoRA in the linear problem and converges to a stationary point of the general nonlinear full fine-tuning. Through extensive experiments across a range of tasks, including commonsense reasoning, arithmetic reasoning, code generation, and safety alignment, we show that fine-tuning only diagonal blocks is sufficient for strong and consistent performance. DiaBlo not only achieves competitive accuracy but also preserves high memory efficiency and fast fine-tuning speed. Codes are available at https://github.com/ziyangjoy/DiaBlo.
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Multi-Modal Sensing and Fusion in mmWave Beamforming for Connected Vehicles: A Transformer Based Framework

βœ‡cs.AI, q-bio.NC updates on arXiv.org
By: Muhammad Baqer Mollah Β· Honggang Wang Β· Mohammad Ataul Karim Β· Hua Fang
arXiv:2602.13606v1 Announce Type: cross Abstract: Millimeter wave (mmWave) communication, utilizing beamforming techniques to address the inherent path loss limitation, is considered as one of the key technologies to support ever increasing high throughput and low latency demands of connected vehicles. However, adopting standard defined beamforming approach in highly dynamic vehicular environments often incurs high beam training overheads and reduction in the available airtime for communications, which is mainly due to exchanging pilot signals and exhaustive beam measurements. To this end, we present a multi-modal sensing and fusion learning framework as a potential alternative solution to reduce such overheads. In this framework, we first extract the representative features from the sensing modalities by modality specific encoders, then, utilize multi-head cross-modal attention to learn dependencies and correlations between different modalities, and subsequently fuse the multimodal features to obtain predicted top-k beams so that the best line-of-sight links can be proactively established. To show the generalizability of the proposed framework, we perform a comprehensive experiment in four different vehicle-to-infrastructure (V2I) and vehicle-to-vehicle (V2V) scenarios from real world multimodal and 60 GHz mmWave wireless sensing data. The experiment reveals that the proposed framework (i) achieves up to 96.72% accuracy on predicting top-15 beams correctly, (ii) incurs roughly 0.77 dB average power loss, and (iii) improves the overall latency and beam searching space overheads by 86.81% and 76.56% respectively for top-15 beams compared to standard defined approach.
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