Multi-Omics-Enabled Precision Strategies for Overcoming CAR-T Therapy Limitations in Gastrointestinal Malignancies

By: Ke Su · Zunyuan Tan · Han Li · Kai You · Susu Xiao · Haiqing Chen · Danyang Li · Xin Liu · Xinrui Du · Jiaxin Hu · Kun He · Yantian Xu · Jian Chen · Yunwei Han

10 September 2026 at 18:00

Biofactors. 2026 Sep-Oct;52(5):e70150. doi: 10.1002/biof.70150.

ABSTRACT

Gastrointestinal malignancies, including gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma, remain major causes of cancer-related morbidity and mortality worldwide. Although chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, its efficacy in gastrointestinal solid tumors remains limited by antigen heterogeneity, insufficient trafficking and infiltration, immunosuppressive tumor microenvironments, on-target off-tumor toxicity, and adaptive resistance. In this review, we summarize the current landscape of CAR-T therapy in gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic cancer, with a focus on representative target antigens and emerging biomarker strategies. We further discuss two major categories of biomarkers: target antigen-related biomarkers and conventional dynamic biomarkers, including serum tumor markers, cytokine changes, CAR-T expansion kinetics, and antigen-loss monitoring. In addition, we highlight how single-cell ribonucleic acid sequencing and spatial transcriptomics provide complementary insights into cellular states, immune exhaustion, stromal barriers, and spatially restricted immune exclusion. By integrating these multi-omics approaches with biomarker-guided patient stratification and next-generation CAR-T engineering, gastrointestinal solid tumor CAR-T therapy may evolve from empirical optimization toward mechanism-driven and precision-guided clinical translation.

PMID:42717494 | PMC:PMC13558850 | DOI:10.1002/biof.70150

Multi-Omics-Enabled Precision Strategies for Overcoming CAR-T Therapy Limitations in Gastrointestinal Malignancies

(Multiomics OR Omics) AND (Pancreatic)

By: Ke Su · Zunyuan Tan · Han Li · Kai You · Susu Xiao · Haiqing Chen · Danyang Li · Xin Liu · Xinrui Du · Jiaxin Hu · Kun He · Yantian Xu · Jian Chen · Yunwei Han

10 September 2026 at 18:00

Biofactors. 2026 Sep-Oct;52(5):e70150. doi: 10.1002/biof.70150.

ABSTRACT

Gastrointestinal malignancies, including gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma, remain major causes of cancer-related morbidity and mortality worldwide. Although chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, its efficacy in gastrointestinal solid tumors remains limited by antigen heterogeneity, insufficient trafficking and infiltration, immunosuppressive tumor microenvironments, on-target off-tumor toxicity, and adaptive resistance. In this review, we summarize the current landscape of CAR-T therapy in gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic cancer, with a focus on representative target antigens and emerging biomarker strategies. We further discuss two major categories of biomarkers: target antigen-related biomarkers and conventional dynamic biomarkers, including serum tumor markers, cytokine changes, CAR-T expansion kinetics, and antigen-loss monitoring. In addition, we highlight how single-cell ribonucleic acid sequencing and spatial transcriptomics provide complementary insights into cellular states, immune exhaustion, stromal barriers, and spatially restricted immune exclusion. By integrating these multi-omics approaches with biomarker-guided patient stratification and next-generation CAR-T engineering, gastrointestinal solid tumor CAR-T therapy may evolve from empirical optimization toward mechanism-driven and precision-guided clinical translation.

PMID:42717494 | PMC:PMC13558850 | DOI:10.1002/biof.70150

Benchmarking the Limits of In-Context Reinforcement Learning for Ad-Hoc Teamwork

cs.AI, q-bio.NC updates on arXiv.org

By: Yuheng Jing · Kai Li · Ziwen Zhang · Jiajun Zhang · Zeyao Ma · Jiaxi Yang · Lei Zhang · Zhe Wu · Jinmin He · Junliang Xing · Jian Cheng

26 May 2026 at 12:00

arXiv:2605.24423v1 Announce Type: new Abstract: In-Context Reinforcement Learning (ICRL) has enabled foundation agents to adapt instantaneously to novel tasks, yet its efficacy in Ad-Hoc Teamwork (AHT)-where coordination with unknown partners is required-remains unexplored. To rigorously evaluate this, we introduce a large-scale benchmark ICRL4AHT, built upon a high-throughput JAX implementation of Overcooked-V2. Our benchmark includes a large, diverse teammate suite spanning both RL and heuristic policies, enabling controlled train-test shifts, and provides a reproducible end-to-end pipeline for teammate generation, learning-history collection, dataset construction, and online multi-episode evaluation. We evaluate representative history-conditioned ICRL algorithms, including Algorithm Distillation (AD) and Decision-Pretrained Transformer (DPT), across millions of transitions. Results reveal notable limitations: contrary to their success in single-agent domains, these baselines fail to exhibit robust test-time adaptation in multi-agent settings. Specifically, these methods frequently underperform random baselines across both unseen teammate and unseen layout tracks, with no clear in-context improvement over long horizons. These findings highlight the challenges of strategic inference under partial observability within the OvercookedV2 AHT protocol, establishing our benchmark as a critical testbed for next-generation coordination algorithms.

ORBIT: Scalable and Verifiable Data Generation for Search Agents on a Tight Budget

cs.AI, q-bio.NC updates on arXiv.org

By: Nandan Thakur · Zijian Chen · Xueguang Ma · Jimmy Lin

3 April 2026 at 12:00

arXiv:2604.01195v2 Announce Type: replace-cross Abstract: Search agents, which integrate language models (LMs) with web search, are becoming crucial for answering complex user queries. Constructing training datasets for deep research tasks, involving multi-step retrieval and reasoning, remains challenging due to expensive human annotation, or cumbersome prerequisites. In this work, we introduce ORBIT, a training dataset with 20K reasoning-intensive queries with short verifiable answers, generated using a frugal framework without relying on paid API services. The modular framework relies on four stages: seed creation, question-answer pair generation, and two stages of verification: self and external. ORBIT spans 15 domains and each training pair requires 4-5 reasoning steps, with external search verification required from the complete web. We train Qwen3-4B as the base model on ORBIT using GRPO and evaluate it on Wikipedia question answering tasks. Extensive experiment results demonstrate that ORBIT-4B achieves strong performance among sub-4B LLMs as search agents, proving the utility of synthetic datasets. Our framework, code and datasets are open-sourced and available publicly.

ST-GDance++: A Scalable Spatial-Temporal Diffusion for Long-Duration Group Choreography

cs.AI, q-bio.NC updates on arXiv.org

By: Jing Xu · Weiqiang Wang · Cunjian Chen · Jun Liu · Qiuhong Ke

25 March 2026 at 12:00

arXiv:2603.22316v1 Announce Type: cross Abstract: Group dance generation from music requires synchronizing multiple dancers while maintaining spatial coordination, making it highly relevant to applications such as film production, gaming, and animation. Recent group dance generation models have achieved promising generation quality, but they remain difficult to deploy in interactive scenarios due to bidirectional attention dependencies. As the number of dancers and the sequence length increase, the attention computation required for aligning music conditions with motion sequences grows quadratically, leading to reduced efficiency and increased risk of motion collisions. Effectively modeling dense spatial-temporal interactions is therefore essential, yet existing methods often struggle to capture such complexity, resulting in limited scalability and unstable multi-dancer coordination. To address these challenges, we propose ST-GDance++, a scalable framework that decouples spatial and temporal dependencies to enable efficient and collision-aware group choreography generation. For spatial modeling, we introduce lightweight distance-aware graph convolutions to capture inter-dancer relationships while reducing computational overhead. For temporal modeling, we design a diffusion noise scheduling strategy together with an efficient temporal-aligned attention mask, enabling stream-based generation for long motion sequences and improving scalability in long-duration scenarios. Experiments on the AIOZ-GDance dataset show that ST-GDance++ achieves competitive generation quality with significantly reduced latency compared to existing methods.

Scale-PINN: Learning Efficient Physics-Informed Neural Networks Through Sequential Correction

cs.AI, q-bio.NC updates on arXiv.org

By: Pao-Hsiung Chiu · Jian Cheng Wong · Chin Chun Ooi · Chang Wei · Yuchen Fan · Yew-Soon Ong

24 February 2026 at 13:00

arXiv:2602.19475v1 Announce Type: cross Abstract: Physics-informed neural networks (PINNs) have emerged as a promising mesh-free paradigm for solving partial differential equations, yet adoption in science and engineering is limited by slow training and modest accuracy relative to modern numerical solvers. We introduce the Sequential Correction Algorithm for Learning Efficient PINN (Scale-PINN), a learning strategy that bridges modern physics-informed learning with numerical algorithms. Scale-PINN incorporates the iterative residual-correction principle, a cornerstone of numerical solvers, directly into the loss formulation, marking a paradigm shift in how PINN losses can be conceived and constructed. This integration enables Scale-PINN to achieve unprecedented convergence speed across PDE problems from different physics domain, including reducing training time on a challenging fluid-dynamics problem for state-of-the-art PINN from hours to sub-2 minutes while maintaining superior accuracy, and enabling application to representative problems in aerodynamics and urban science. By uniting the rigor of numerical methods with the flexibility of deep learning, Scale-PINN marks a significant leap toward the practical adoption of PINNs in science and engineering through scalable, physics-informed learning. Codes are available at https://github.com/chiuph/SCALE-PINN.

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