{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T03:00:24Z","timestamp":1777950024878,"version":"3.51.4"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune checkpoint blockade (ICB) has improved outcomes for a subset of colorectal cancer (CRC) patients, yet the cellular determinants that drive heterogeneous treatment responses remain insufficiently understood. The extent to which ICB reshapes immune populations across tumor, blood, and adjacent normal tissues at single-cell resolution is largely unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We reanalyzed spatiotemporal single-cell RNA-sequencing data from CRC patients treated with Pembrolizumab or Sintilimab, profiling immune and stromal compartments across pre- and post-treatment tumor, blood, and normal mucosa. Major cell types and transcriptional programs were characterized using Seurat and Harmony. Treatment-associated cellular remodeling, differential gene expression, and response-related signatures were assessed in T cells and B cells. Cell-cell communication networks were inferred using CellChat.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ICB produced pronounced remodeling of tumor-infiltrating lymphocytes, particularly within T cell and B cell lineages. Responders (CR\/PR) exhibited robust cytotoxic T-cell activation characterized by up-regulation of GNLY, GZMB, and CXCL13, whereas non-responders (SD) uniquely showed persistent overexpression of HSPA1B, a stress-response gene associated with tumor progression and immune suppression. Responders (CR\/PR) exhibited robust cytotoxic T-cell activation, with increased expression of GNLY, GZMB, and CXCL13. In contrast, non-responders (SD) exhibited persistent overexpression of HSPA1B, a stress-response gene linked to tumor progression and immune suppression. B cells from responders demonstrated strong induction of TXNIP, a regulator of redox balance and inflammasome activity. This suggests a potential association between ICB treatment and a pro-inflammatory B-cell phenotype. Cell-cell communication analysis revealed that responders selectively enhanced CXCL, IL16, and CD22 signaling pathways. This indicates coordinated activation of a T-B-myeloid communication axis, which was absent in SD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This integrative spatiotemporal single-cell analysis reveals that effective ICB responses in CRC are associated with coordinated activation of cytotoxic T cells, TXNIP-associated transcriptional changes in B cells, and strengthening of CXCL-centered immune communication networks. In contrast, HSPA1B-high transcriptional states are associated with treatment resistance. These findings provide mechanistic insights into response heterogeneity and highlight potential candidate targets, such as HSPA1B and CXCR4-associated pathways for improving immunotherapy efficacy in CRC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1840165","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:34:28Z","timestamp":1777872868000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigate the heterogeneity of colorectal cancer patients at the single-cell level prior to and subsequent to immunotherapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Heng","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Hubei Provincial Clinical Research Center for central nervous system repair and functional reconstruction, Taihe Hospital, Hubei University of Medicine","place":["Shiyan, Hubei, China"]},{"name":"Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University","place":["Fuzhou, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Hubei Provincial Clinical Research Center for central nervous system repair and functional reconstruction, Taihe Hospital, Hubei University of Medicine","place":["Shiyan, Hubei, China"]},{"name":"Department of Cerebrovascular Disease Diagnosis and Treatment Center, Taihe Hospital, Hubei University of Medicine","place":["Shiyan, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Hubei Provincial Clinical Research Center for central nervous system repair and functional reconstruction, Taihe Hospital, Hubei University of Medicine","place":["Shiyan, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Hubei Provincial Clinical Research Center for central nervous system repair and functional reconstruction, Taihe Hospital, Hubei University of Medicine","place":["Shiyan, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenkang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Hubei Provincial Clinical Research Center for central nervous system repair and functional reconstruction, Taihe Hospital, Hubei University of Medicine","place":["Shiyan, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Hubei Provincial Clinical Research Center for central nervous system repair and functional reconstruction, Taihe Hospital, Hubei University of Medicine","place":["Shiyan, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Hubei Provincial Clinical Research Center for central nervous system repair and functional reconstruction, Taihe Hospital, Hubei University of Medicine","place":["Shiyan, Hubei, China"]},{"name":"Department of Cerebrovascular Disease Diagnosis and Treatment Center, Taihe Hospital, Hubei University of Medicine","place":["Shiyan, Hubei, China"]},{"name":"Institute of Infection and Immunity, Taihe Hospital, Hubei University of Medicine","place":["Shiyan, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2017699","article-title":"Pembrolizumab in microsatellite-instability-high advanced colorectal cancer","volume":"383","author":"Andr\u00e9","year":"2020","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01440","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update","volume":"39","author":"Schneider","year":"2021","journal-title":"J Clin Oncol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/s41419-019-1638-6","article-title":"Gegen Qinlian decoction enhances the effect of PD-1 blockade in colorectal cancer with microsatellite stability by remodelling the gut microbiota and the tumour microenvironment","volume":"10","author":"Lv","year":"2019","journal-title":"Cell Death Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8209.CD-20-1680","article-title":"The next decade of immune checkpoint therapy","volume":"11","author":"Sharma","year":"2021","journal-title":"Cancer Discov"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-016-9643-z","article-title":"One microenvironment does not fit all: heterogeneity beyond cancer cells","volume":"35","author":"Kim","year":"2016","journal-title":"Cancer Metastasis Rev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3337","article-title":"CSF-1R inhibition alters macrophage polarization and blocks glioma progression","volume":"19","author":"Pyonteck","year":"2013","journal-title":"Nat Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctarc.2025.100872","article-title":"The emerging role of blood-based biomarkers in early detection of colorectal cancer: A systematic review","volume":"42","author":"Shweikeh","year":"2024","journal-title":"Cancer Treat Res Commun"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1186\/s12967-025-06996-0","article-title":"Droplet-based single-cell RNA sequencing: decoding cellular heterogeneity for breakthroughs in cancer, reproduction, and beyond","volume":"23","author":"Luo","year":"2025","journal-title":"J Transl Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1016\/j.ccell.2024.06.009","article-title":"Spatiotemporal single-cell analysis decodes cellular dynamics underlying different responses to immunotherapy in colorectal cancer","volume":"42","author":"Chen","year":"2024","journal-title":"Cancer Cell"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with Harmony","volume":"16","author":"Korsunsky","year":"2019","journal-title":"Nat Methods"},{"key":"B12","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"B13","doi-asserted-by":"publisher","first-page":"6268","DOI":"10.1038\/s41467-020-20019-0","article-title":"Immune suppressive landscape in the human esophageal squamous cell carcinoma microenvironment","volume":"11","author":"Zheng","year":"2020","journal-title":"Nat Commun"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1016\/j.ccell.2021.09.010","article-title":"Single-cell analyses reveal key immune cell subsets associated with response to PD-L1 blockade in triple-negative breast cancer","volume":"39","author":"Zhang","year":"2021","journal-title":"Cancer Cell"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/nri1572","article-title":"Regulation of plasma-cell development","volume":"5","author":"Shapiro-Shelef","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.11.012","article-title":"Granzyme B promotes cytotoxic lymphocyte transmigration via basement membrane remodeling","volume":"41","author":"Prakash","year":"2014","journal-title":"Immunity"},{"key":"B17","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s40259-022-00573-3","article-title":"Targeting co-stimulatory receptors of the TNF superfamily for cancer immunotherapy","volume":"37","author":"M\u00fcller","year":"2023","journal-title":"BioDrugs"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001136","article-title":"CXCL13 shapes immunoactive tumor microenvironment and enhances the efficacy of PD-1 checkpoint blockade in high-grade serous ovarian cancer","volume":"9","author":"Yang","year":"2021","journal-title":"J Immunother Cancer"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201546043","article-title":"TGF-\u03b2 induces the differentiation of human CXCL13-producing CD4+; T cells","volume":"46","author":"Kobayashi","year":"2016","journal-title":"Eur J Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200604000-00009","article-title":"Expression of CXCL13 by neoplastic cells in angioimmunoblastic T-cell lymphoma (AITL): a new diagnostic marker providing evidence that AITL derives from follicular helper T cells","volume":"30","author":"Dupuis","year":"2006","journal-title":"Am J Surg Pathol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.749673","article-title":"Upregulation of HSPA1A\/HSPA1B\/HSPA7 and downregulation of HSPA9 were related to poor survival in colon cancer","volume":"11","author":"Guan","year":"2021","journal-title":"Front Oncol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.568574","article-title":"Research progress of TXNIP as a tumor suppressor gene participating in the metabolic reprogramming and oxidative stress of cancer cells in various cancers","volume":"10","author":"Chen","year":"2020","journal-title":"Front Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472","article-title":"PIK3IP1, a negative regulator of PI3K, suppresses the development of hepatocellular carcinoma","volume":"68","author":"He","year":"2008","journal-title":"Cancer Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell\u2013cell communication using CellChat","volume":"12","author":"Jin","year":"2021","journal-title":"Nat Commun"},{"key":"B25","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1038\/s41420-023-01524-9","article-title":"The role of CXCL family members in different diseases","volume":"9","author":"Zhou","year":"2023","journal-title":"Cell Death Discov"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2024.285304","article-title":"Lymphoma cell-driven IL-16 is expressed in activated B-cell-like diffuse large B-cell lymphomas and regulates the pro-tumor microenvironment","volume":"110","author":"Guan","year":"2025","journal-title":"Haematologica"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.2147\/ITT.S288546","article-title":"Targeting CD22 for the treatment of B-cell Malignancies","volume":"10","author":"Shah","year":"2021","journal-title":"Immunotargets Ther"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000003459","article-title":"Single-cell transcriptome analysis reveals regulatory programs associated with tumor resistance during immunotherapy in colorectal cancer","volume":"10","author":"Chen","year":"2025","journal-title":"Int J Surg"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S531641","article-title":"Integrated single-cell analysis reveals the heterogeneity of tumor-associated macrophages and their implications for immunotherapy in colorectal cancer","volume":"18","author":"Xu","year":"2025","journal-title":"J Inflammation Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1016\/j.ccell.2023.04.011","article-title":"Remodeling of the immune and stromal cell compartment by PD-1 blockade in mismatch repair-deficient colorectal cancer","volume":"41","author":"Li","year":"2023","journal-title":"Cancer Cell"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5526327","article-title":"The prognostic significance of hsp70 in patients with colorectal cancer patients: A PRISMA-compliant meta-analysis","volume":"2021","author":"Gao","year":"2021","journal-title":"BioMed Res Int"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2024.2400314","article-title":"Tertiary lymphoid structures in colorectal cancer","volume":"56","author":"Lv","year":"2024","journal-title":"Ann Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.08.009","article-title":"Tertiary lymphoid structures and B cells: An intratumoral immunity cycle","volume":"56","author":"Fridman","year":"2023","journal-title":"Immunity"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-023-02442-4","article-title":"The role of TXNIP in cancer: a fine balance between redox, metabolic, and immunological tumor control","volume":"129","author":"Deng","year":"2023","journal-title":"Br J Cancer"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2025.189394","article-title":"TXNIP in cancer: Unlocking biological insights and tackling clinical challenges","volume":"1880","author":"Del Console","year":"2025","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1548509","article-title":"Glucose deprivation and identification of TXNIP as an immunometabolic modulator of T cell activation in cancer","volume":"16","author":"Dubuisson","year":"2025","journal-title":"Front Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2023.101828","article-title":"Lipid metabolism-associated genes serve as potential predictive biomarkers in neoadjuvant chemoradiotherapy combined with immunotherapy in rectal cancer","volume":"39","author":"Peng","year":"2024","journal-title":"Transl Oncol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2025.217571","article-title":"Therapy resistance: Modulating evolutionarily conserved heat shock protein machinery in cancer","volume":"616","author":"Skrabalak","year":"2025","journal-title":"Cancer Lett"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13194753","article-title":"Overcoming immunotherapy resistance by targeting the tumor-intrinsic NLRP3-HSP70 signaling axis","volume":"13","author":"Theivanthiran","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e37511","article-title":"Single-cell RNA sequencing analysis reveals the distinct features of colorectal cancer with or without Fusobacterium nucleatum infection in PD-L1 blockade therapy","volume":"10","author":"Ding","year":"2024","journal-title":"Heliyon"},{"key":"B41","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/s41392-024-01868-3","article-title":"Targeting cytokine and chemokine signaling pathways for cancer therapy","volume":"9","author":"Yi","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"B42","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1007\/s12672-025-01842-7","article-title":"Integration of single-cell and bulk RNA-sequencing data to construct and validate a signature based on NK cell marker genes to predict immunotherapy response and prognosis in colorectal cancer","volume":"16","author":"Qin","year":"2025","journal-title":"Discov Oncol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"20177","DOI":"10.1038\/s41598-024-70422-6","article-title":"Integrated single-cell and bulk RNA-seq analysis identifies a prognostic T-cell signature in colorectal cancer","volume":"14","author":"Cui","year":"2024","journal-title":"Sci Rep"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2023.07.005","article-title":"Single-cell dissection of tumor microenvironmental response and resistance to cancer therapy","volume":"39","author":"Luo","year":"2023","journal-title":"Trends Genet"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2025-013763","article-title":"Single-cell and spatial transcriptome profiling identifies the immunosuppressive spatial niche in KRAS-mutant colorectal cancer","volume":"13","author":"Yang","year":"2025","journal-title":"J Immunother Cancer"},{"key":"B46","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1038\/s41698-025-01187-y","article-title":"Comprehensive single-cell transcriptome landscape of metastatic colorectal cancer identifies budding-potential cells and their interactions with cancer-associated fibroblasts","volume":"9","author":"Ma","year":"2025","journal-title":"NPJ Precis Oncol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s40364-025-00888-7","article-title":"Single-cell RNA sequencing unveils enhanced antitumor immunity in colorectal cancer with PD-1 blockade and LINC00673 deletion","volume":"14","author":"Zhu","year":"2026","journal-title":"biomark Res"},{"key":"B48","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1007\/s00262-025-04173-2","article-title":"The single-cell atlas of colorectal cancer reveals cellular heterogeneity and key molecular features of the tumor immune microenvironment","volume":"74","author":"Li","year":"2025","journal-title":"Cancer Immunol Immunother"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105154","article-title":"T cell exhaustion initiates tertiary lymphoid structures and turbocharges cancer-immunity cycle","volume":"104","author":"Lin","year":"2024","journal-title":"EBioMedicine"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.884839","article-title":"Tumor microenvironment heterogeneity-based score system predicts clinical prognosis and response to immune checkpoint blockade in multiple colorectal cancer cohorts","volume":"9","author":"Wang","year":"2022","journal-title":"Front Mol Biosci"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1259461","article-title":"Advances in immunotyping of colorectal cancer","volume":"14","author":"Wu","year":"2023","journal-title":"Front Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2025.217491","article-title":"Tertiary lymphoid structures as a biomarker in immunotherapy and beyond: Advancing towards clinical application","volume":"613","author":"Cui","year":"2025","journal-title":"Cancer Lett"},{"key":"B53","doi-asserted-by":"publisher","first-page":"10259","DOI":"10.1038\/s41467-024-54710-3","article-title":"Spatially organized tumor-stroma boundary determines the efficacy of immunotherapy in colorectal cancer patients","volume":"15","author":"Feng","year":"2024","journal-title":"Nat Commun"},{"key":"B54","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1038\/s41698-025-01129-8","article-title":"Single-cell integration analysis reveals molecular signatures of the tumor microenvironment in early-onset colorectal cancer","volume":"9","author":"Peng","year":"2025","journal-title":"NPJ Precis Oncol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/s41419-025-07471-w","article-title":"High baseline levels of PD-L1 reduce the heterogeneity of immune checkpoint signature and sensitize anti-PD1 therapy in lung and colorectal cancers","volume":"16","author":"Fan","year":"2025","journal-title":"Cell Death Dis"},{"key":"B56","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1186\/s12935-025-03765-3","article-title":"CXCL2: a key player in the tumor microenvironment and inflammatory diseases","volume":"25","author":"Lv","year":"2025","journal-title":"Cancer Cell Int"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1007\/s12672-025-02794-8","article-title":"Adaptive immune changes in colorectal cancer: a focus on T and B cell activation genes","volume":"16","author":"Rady","year":"2025","journal-title":"Discov Oncol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.217096","article-title":"Gut microbial metabolites in lung cancer development and immunotherapy: Novel insights into gut-lung axis","volume":"598","author":"Li","year":"2024","journal-title":"Cancer Lett"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1840165\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:34:29Z","timestamp":1777872869000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1840165\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,4]]},"references-count":58,"alternative-id":["10.3389\/fimmu.2026.1840165"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1840165","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,4]]},"article-number":"1840165"}}