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A Comprehensive Survey on Reinforcement Learning-based Agentic Search: Foundations, Roles, Optimizations, Evaluations, and Applications

arXiv:2510.16724v2 Announce Type: replace Abstract: The advent of large language models (LLMs) has transformed information access and reasoning through open-ended natural language interaction. However, LLMs remain limited by static knowledge, factual hallucinations, and the inability to retrieve real-time or domain-specific information. Retrieval-Augmented Generation (RAG) mitigates these issues by grounding model outputs in external evidence, but traditional RAG pipelines are often single turn and heuristic, lacking adaptive control over retrieval and reasoning. Recent advances in agentic search address these limitations by enabling LLMs to plan, retrieve, and reflect through multi-step interaction with search environments. Within this paradigm, reinforcement learning (RL) offers a powerful mechanism for adaptive and self-improving search behavior. This survey provides the first comprehensive overview of \emph{RL-based agentic search}, organizing the emerging field along three complementary dimensions: (i) What RL is for (functional roles), (ii) How RL is used (optimization strategies), and (iii) Where RL is applied (scope of optimization). We summarize representative methods, evaluation protocols, and applications, and discuss open challenges and future directions toward building reliable and scalable RL driven agentic search systems. We hope this survey will inspire future research on the integration of RL and agentic search. Our repository is available at https://github.com/ventr1c/Awesome-RL-based-Agentic-Search-Papers.
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Decoding the tumor immune microenvironment in lung squamous cell carcinoma: characteristics, regulatory mechanisms, and future directions in immunotherapy

Transl Lung Cancer Res. 2025 Sep 30;14(9):4112-4130. doi: 10.21037/tlcr-2025-350. Epub 2025 Sep 18.

ABSTRACT

Lung squamous cell carcinoma (LUSC), a predominant type of lung cancer, is marked by an unfavorable prognosis and limited therapeutic options. Unlike lung adenocarcinoma (LUAD), LUSC exhibits few driver mutations, resulting in minimal benefits from targeted therapies for these patients. Despite the transformative effects of immunotherapy on patient outcomes, only a subset of patients achieving durable responses. This heterogeneity in treatment outcomes is increasingly attributed to the complex feature of the tumor immune microenvironment (TIME) in LUSC. The TIME of LUSC is a highly dynamic ecosystem composed of diverse immune cell populations and stromal components that collectively foster an immune-evasive niche. Recent breakthroughs in multi-omics technologies, particularly single-cell RNA sequencing (scRNA-seq) and spatial omics, have provided unprecedented resolution in dissecting the cellular and molecular architecture of the TIME in LUSC. These technologies have enabled the identification of distinct immune cells and their spatial interactions with the tumor, shedding light on the mechanisms underlying immune evasion and resistance to immunotherapy. Building on these advancements, this review establishes a new classification of the TIME which may guide patient stratification and personalized immunotherapy. And we comprehensively offer a detailed examination of the principal characteristics and regulatory mechanisms of the TIME, highlighting potential immunotherapeutic strategies tailored to this distinct immunological context.

PMID:41133013 | PMC:PMC12541881 | DOI:10.21037/tlcr-2025-350

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A multiomics dataset of paired CT image and plasma cell-free DNA end motif for patients with pulmonary nodules

Sci Data. 2025 Apr 1;12(1):545. doi: 10.1038/s41597-025-04912-1.

ABSTRACT

Diagnosing lung cancer at a curable stage offers the opportunity for a favorable prognosis. The emerging epigenomics analysis on plasma cell-free DNA (cfDNA), including 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) modifications, has acted as a promising approach facilitating the identification of lung cancer. And, integrating 5mC biomarker with chest computed tomography (CT) image features could optimize the diagnosis of lung cancer, exceeding the performance of models built on single feature. However, the clinical applicability of integrated markers might be limited by the potential risk of overfitting due to small sample size. Hence, we prospectively collected peripheral blood sample and the paired chest CT images of 2032 patients with indeterminate pulmonary nodules across 5 centers, and constructed a large-scale, multi-institutional, multiomics database that encompass CT imaging data and plasma cfDNA fragmentomic in 5mC-, 5hmC-enriched regions. To our best knowledge, this dataset is the first radio-epigenomic dataset with the largest sample size, and provides multi-dimensional insights for early diagnosis of lung cancer, facilitating the individuated management for lung cancer.

PMID:40169596 | PMC:PMC11961589 | DOI:10.1038/s41597-025-04912-1

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WNT2–SOX4 positive feedback loop promotes chemoresistance and tumorigenesis by inducing stem-cell like properties in gastric cancer

Oncogene, Published online: 26 August 2023; doi:10.1038/s41388-023-02816-1

WNT2–SOX4 positive feedback loop promotes chemoresistance and tumorigenesis by inducing stem-cell like properties in gastric cancer
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