{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T11:29:18Z","timestamp":1787052558361,"version":"build-2736575974"},"reference-count":90,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":84,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-026-10336-3","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:06:06Z","timestamp":1779753966000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ICIsAtlas reveals a suppressive NK cell niche in pan-cancer immunotherapy profiles"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8716-2840","authenticated-orcid":false,"given":"Yumo","family":"Xie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haotian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyi","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziying","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingrong","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixiao","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peisi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puning","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3260-2343","authenticated-orcid":false,"given":"Xiaoxia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7579-2987","authenticated-orcid":false,"given":"Linping","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5200-3997","authenticated-orcid":false,"given":"Yanxin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3911-6911","authenticated-orcid":false,"given":"Xiaolin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8357-1615","authenticated-orcid":false,"given":"Huichuan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"10336_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.immuni.2013.07.012","volume":"39","author":"DS Chen","year":"2013","unstructured":"Chen, D. S. & Mellman, I. Oncology meets immunology: the cancer-immunity cycle. Immunity 39, 1\u201310 (2013).","journal-title":"Immunity"},{"key":"10336_CR2","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.1056\/NEJMoa1200690","volume":"366","author":"SL Topalian","year":"2012","unstructured":"Topalian, S. L. et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366, 2443\u20132454 (2012).","journal-title":"N. Engl. J. Med."},{"key":"10336_CR3","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1056\/NEJMoa1613683","volume":"376","author":"J Bellmunt","year":"2017","unstructured":"Bellmunt, J. et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N. Engl. J. Med. 376, 1015\u20131026 (2017).","journal-title":"N. Engl. J. Med."},{"key":"10336_CR4","doi-asserted-by":"publisher","first-page":"2207","DOI":"10.1056\/NEJMoa2017699","volume":"383","author":"T Andr\u00e9","year":"2020","unstructured":"Andr\u00e9, T. et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N. Engl. J. Med. 383, 2207\u20132218 (2020).","journal-title":"N. Engl. J. Med."},{"key":"10336_CR5","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1200\/JCO.2014.56.2736","volume":"33","author":"D Schadendorf","year":"2015","unstructured":"Schadendorf, D. et al. Pooled analysis of long-term survival data from Phase II and Phase III trials of ipilimumab in unresectable or metastatic melanoma. J. Clin. Oncol. 33, 1889\u20131894 (2015).","journal-title":"J. Clin. Oncol."},{"key":"10336_CR6","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1001\/jamaoncol.2019.1549","volume":"5","author":"S Lu","year":"2019","unstructured":"Lu, S. et al. Comparison of biomarker modalities for predicting response to PD-1\/PD-L1 checkpoint blockade: a systematic review and meta-analysis. JAMA Oncol. 5, 1195\u20131204 (2019).","journal-title":"JAMA Oncol."},{"key":"10336_CR7","doi-asserted-by":"publisher","first-page":"e542","DOI":"10.1016\/S1470-2045(16)30406-5","volume":"17","author":"GT Gibney","year":"2016","unstructured":"Gibney, G. T., Weiner, L. M. & Atkins, M. B. Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol. 17, e542\u2013e551 (2016).","journal-title":"Lancet Oncol."},{"key":"10336_CR8","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1158\/2159-8290.CD-15-1545","volume":"6","author":"PL Chen","year":"2016","unstructured":"Chen, P. L. et al. Analysis of immune signatures in longitudinal tumor samples yields insight into biomarkers of response and mechanisms of resistance to immune checkpoint blockade. Cancer Discov. 6, 827\u2013837 (2016).","journal-title":"Cancer Discov."},{"key":"10336_CR9","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1038\/nature13954","volume":"515","author":"PC Tumeh","year":"2014","unstructured":"Tumeh, P. C. et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515, 568\u2013571 (2014).","journal-title":"Nature"},{"key":"10336_CR10","doi-asserted-by":"publisher","first-page":"2685","DOI":"10.1158\/0008-5472.CAN-08-2654","volume":"69","author":"M Camus","year":"2009","unstructured":"Camus, M. et al. Coordination of intratumoral immune reaction and human colorectal cancer recurrence. Cancer Res. 69, 2685\u20132693 (2009).","journal-title":"Cancer Res."},{"key":"10336_CR11","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/nature21349","volume":"541","author":"DS Chen","year":"2017","unstructured":"Chen, D. S. & Mellman, I. Elements of cancer immunity and the cancer-immune set point. Nature 541, 321\u2013330 (2017).","journal-title":"Nature"},{"key":"10336_CR12","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/s41573-018-0007-y","volume":"18","author":"J Galon","year":"2019","unstructured":"Galon, J. & Bruni, D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat. Rev. Drug Discov. 18, 197\u2013218 (2019).","journal-title":"Nat. Rev. Drug Discov."},{"key":"10336_CR13","doi-asserted-by":"publisher","first-page":"e419","DOI":"10.1016\/S1470-2045(20)30234-5","volume":"21","author":"M Ochoa de Olza","year":"2020","unstructured":"Ochoa de Olza, M., Navarro Rodrigo, B., Zimmermann, S. & Coukos, G. Turning up the heat on non-immunoreactive tumours: opportunities for clinical development. Lancet Oncol. 21, e419\u2013e430 (2020).","journal-title":"Lancet Oncol."},{"key":"10336_CR14","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/s41587-019-0114-2","volume":"37","author":"AM Newman","year":"2019","unstructured":"Newman, A. M. et al. Determining cell type abundance and expression from bulk tissues with digital cytometry. Nat. Biotechnol. 37, 773\u2013782 (2019).","journal-title":"Nat. Biotechnol."},{"key":"10336_CR15","doi-asserted-by":"publisher","first-page":"5482","DOI":"10.1016\/j.cell.2021.09.014","volume":"184","author":"BA Luca","year":"2021","unstructured":"Luca, B. A. et al. Atlas of clinically distinct cell states and ecosystems across human solid tumors. Cell 184, 5482\u20135496.e28 (2021).","journal-title":"Cell"},{"key":"10336_CR16","doi-asserted-by":"publisher","first-page":"S279","DOI":"10.1093\/bioinformatics\/17.suppl_1.S279","volume":"17","author":"D Venet","year":"2001","unstructured":"Venet, D., Pecasse, F., Maenhaut, C. & Bersini, H. Separation of samples into their constituents using gene expression data. Bioinformatics 17, S279\u2013S287 (2001).","journal-title":"Bioinformatics"},{"key":"10336_CR17","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nmeth.3337","volume":"12","author":"AM Newman","year":"2015","unstructured":"Newman, A. M. et al. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods 12, 453\u2013457 (2015).","journal-title":"Nat. Methods"},{"key":"10336_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-1070-5","volume":"17","author":"E Becht","year":"2016","unstructured":"Becht, E. et al. Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression. Genome Biol. 17, 218 (2016). England.","journal-title":"Genome Biol."},{"key":"10336_CR19","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1158\/2159-8290.CD-21-0887","volume":"12","author":"K Wang","year":"2022","unstructured":"Wang, K. et al. Deconvolving clinically relevant cellular immune cross-talk from bulk gene expression using CODEFACS and LIRICS stratifies patients with melanoma to anti-PD-1 therapy. Cancer Discov. 12, 1088\u20131105 (2022).","journal-title":"Cancer Discov."},{"key":"10336_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.crmeth.2025.100985","volume":"5","author":"M van Santvoort","year":"2025","unstructured":"van Santvoort, M. et al. Mathematically mapping the network of cells in the tumor microenvironment. Cell Rep. Methods 5, 100985 (2025).","journal-title":"Cell Rep. Methods"},{"key":"10336_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52555-4","volume":"15","author":"S Sahni","year":"2024","unstructured":"Sahni, S. et al. A machine learning model reveals expansive downregulation of ligand-receptor interactions that enhance lymphocyte infiltration in melanoma with developed resistance to immune checkpoint blockade. Nat. Commun. 15, 8867 (2024).","journal-title":"Nat. Commun."},{"key":"10336_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9","volume":"12","author":"S Jin","year":"2021","unstructured":"Jin, S. et al. Inference and analysis of cell\u2013cell communication using CellChat. Nat. Commun. 12, 1088 (2021).","journal-title":"Nat. Commun."},{"key":"10336_CR23","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/s41591-020-1133-8","volume":"27","author":"J Park","year":"2021","unstructured":"Park, J. et al. Exome-wide evaluation of rare coding variants using electronic health records identifies new gene\u2013phenotype associations. Nat. Med. 27, 66\u201372 (2021).","journal-title":"Nat. Med."},{"key":"10336_CR24","doi-asserted-by":"publisher","first-page":"e1002606","DOI":"10.1371\/journal.pcbi.1002606","volume":"8","author":"K Faust","year":"2012","unstructured":"Faust, K. et al. Microbial co-occurrence relationships in the human microbiome. PLoS Comput. Biol. 8, e1002606 (2012).","journal-title":"PLoS Comput. Biol."},{"key":"10336_CR25","doi-asserted-by":"publisher","first-page":"4235","DOI":"10.1016\/j.cell.2023.07.034","volume":"186","author":"F Tang","year":"2023","unstructured":"Tang, F. et al. A pan-cancer single-cell panorama of human natural killer cells. Cell 186, 4235\u20134251.e20 (2023).","journal-title":"Cell"},{"key":"10336_CR26","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1038\/nm1452","volume":"12","author":"J Hanna","year":"2006","unstructured":"Hanna, J. et al. Decidual NK cells regulate key developmental processes at the human fetal\u2013maternal interface. Nat. Med 12, 1065\u20131074 (2006).","journal-title":"Nat. Med"},{"key":"10336_CR27","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1158\/1535-7163.MCT-16-0676","volume":"16","author":"AJ Garton","year":"2017","unstructured":"Garton, A. J. et al. Anti-KIT monoclonal antibody treatment enhances the antitumor activity of immune checkpoint inhibitors by reversing tumor-induced immunosuppression. Mol. Cancer Ther. 16, 671\u2013680 (2017).","journal-title":"Mol. Cancer Ther."},{"key":"10336_CR28","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/nrclinonc.2018.29","volume":"15","author":"D Fukumura","year":"2018","unstructured":"Fukumura, D., Kloepper, J., Amoozgar, Z., Duda, D. G. & Jain, R. K. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat. Rev. Clin. Oncol. 15, 325\u2013340 (2018).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10336_CR29","doi-asserted-by":"crossref","unstructured":"Hinterbrandner, M. et al. Tnfrsf4-expressing regulatory T cells promote immune escape of chronic myeloid leukemia stem cells. JCI Insight 6, e151797 (2021).","DOI":"10.1172\/jci.insight.151797"},{"key":"10336_CR30","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.smim.2018.02.003","volume":"37","author":"M Kolev","year":"2018","unstructured":"Kolev, M. & Markiewski, M. M. Targeting complement-mediated immunoregulation for cancer immunotherapy. Semin. Immunol. 37, 85\u201397 (2018).","journal-title":"Semin. Immunol."},{"key":"10336_CR31","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1002\/jcp.30534","volume":"237","author":"J Yang","year":"2022","unstructured":"Yang, J. et al. Emerging roles of angiopoietin-like proteins in inflammation: mechanisms and potential as pharmacological targets. J. Cell. Physiol. 237, 98\u2013117 (2022).","journal-title":"J. Cell. Physiol."},{"key":"10336_CR32","doi-asserted-by":"publisher","first-page":"2697","DOI":"10.1111\/febs.15829","volume":"288","author":"A Chandrabalan","year":"2021","unstructured":"Chandrabalan, A. & Ramachandran, R. Molecular mechanisms regulating proteinase-activated receptors (PARs). FEBS J. 288, 2697\u20132726 (2021).","journal-title":"FEBS J."},{"key":"10336_CR33","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.celrep.2016.12.019","volume":"18","author":"P Charoentong","year":"2017","unstructured":"Charoentong, P. et al. Pan-cancer immunogenomic analyses reveal genotype\u2013immunophenotype relationships and predictors of response to checkpoint blockade. Cell Rep. 18, 248\u2013262 (2017).","journal-title":"Cell Rep."},{"key":"10336_CR34","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1038\/s41591-018-0136-1","volume":"24","author":"P Jiang","year":"2018","unstructured":"Jiang, P. et al. Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response. Nat. Med. 24, 1550\u20131558 (2018).","journal-title":"Nat. Med."},{"key":"10336_CR35","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1158\/0008-5472.CAN-21-2335","volume":"82","author":"J Yang","year":"2021","unstructured":"Yang, J. et al. A pan-cancer immunogenomic atlas for immune checkpoint blockade immunotherapy. Cancer Res. 82, 539\u2013542 (2021).","journal-title":"Cancer Res."},{"key":"10336_CR36","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1038\/s42003-025-08457-2","volume":"8","author":"T Liu","year":"2025","unstructured":"Liu, T. et al. Deciphering cancer therapy resistance via patient-level single-cell transcriptomics with CellResDB. Commun. Biol. 8, 1049 (2025).","journal-title":"Commun. Biol."},{"key":"10336_CR37","doi-asserted-by":"crossref","unstructured":"Kang, H, et al. A Comprehensive Benchmark of Transcriptomic Biomarkers for Immune Checkpoint Blockades. Cancers (Basel) 15, 4094 (2023).","DOI":"10.3390\/cancers15164094"},{"key":"10336_CR38","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1016\/j.annonc.2022.08.084","volume":"33","author":"Y Bareche","year":"2022","unstructured":"Bareche, Y. et al. Leveraging big data of immune checkpoint blockade response identifies novel potential targets. Ann. Oncol. 33, 1304\u20131317 (2022).","journal-title":"Ann. Oncol."},{"key":"10336_CR39","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/j.medj.2023.07.006","volume":"4","author":"A Hernando-Calvo","year":"2023","unstructured":"Hernando-Calvo, A. et al. A pan-cancer clinical platform to predict immunotherapy outcomes and prioritize immuno-oncology combinations in early-phase trials. Med 4, 710\u2013727.e5 (2023).","journal-title":"Med"},{"key":"10336_CR40","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1158\/2767-9764.CRC-23-0442","volume":"4","author":"YA Guo","year":"2024","unstructured":"Guo, Y. A. et al. Transcriptome deconvolution reveals absence of cancer cell expression signature in immune checkpoint blockade response. Cancer Res. Commun. 4, 1581\u20131596 (2024).","journal-title":"Cancer Res. Commun."},{"key":"10336_CR41","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1038\/s41568-019-0235-4","volume":"20","author":"AM van der Leun","year":"2020","unstructured":"van der Leun, A. M., Thommen, D. S. & Schumacher, T. N. CD8+ T cell states in human cancer: insights from single-cell analysis. Nat. Rev. Cancer 20, 218\u2013232 (2020).","journal-title":"Nat. Rev. Cancer"},{"key":"10336_CR42","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nature19330","volume":"537","author":"SJ Im","year":"2016","unstructured":"Im, S. J. et al. Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Nature 537, 417\u2013421 (2016).","journal-title":"Nature"},{"key":"10336_CR43","doi-asserted-by":"crossref","unstructured":"Ahmadzadeh, M. et al. Tumor-infiltrating human CD4+ regulatory T cells display a distinct TCR repertoire and exhibit tumor and neoantigen reactivity. Sci. Immunol. 4, eaao4310 (2019).","DOI":"10.1126\/sciimmunol.aao4310"},{"key":"10336_CR44","doi-asserted-by":"publisher","first-page":"5309","DOI":"10.1016\/j.cell.2021.09.020","volume":"184","author":"G Morad","year":"2021","unstructured":"Morad, G., Helmink, B. A., Sharma, P. & Wargo, J. A. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade. Cell 184, 5309\u20135337 (2021).","journal-title":"Cell"},{"key":"10336_CR45","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/nature18945","volume":"536","author":"EM Verdegaal","year":"2016","unstructured":"Verdegaal, E. M. et al. Neoantigen landscape dynamics during human melanoma-T cell interactions. Nature 536, 91\u201395 (2016).","journal-title":"Nature"},{"key":"10336_CR46","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/s41588-018-0312-8","volume":"51","author":"RM Samstein","year":"2019","unstructured":"Samstein, R. M. et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat. Genet. 51, 202\u2013206 (2019).","journal-title":"Nat. Genet."},{"key":"10336_CR47","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/j.annonc.2021.02.006","volume":"32","author":"DJ McGrail","year":"2021","unstructured":"McGrail, D. J. et al. High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types. Ann. Oncol. 32, 661\u2013672 (2021).","journal-title":"Ann. Oncol."},{"key":"10336_CR48","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/s41568-019-0144-6","volume":"19","author":"C Saut\u00e8s-Fridman","year":"2019","unstructured":"Saut\u00e8s-Fridman, C., Petitprez, F., Calderaro, J. & Fridman, W. H. Tertiary lymphoid structures in the era of cancer immunotherapy. Nat. Rev. Cancer 19, 307\u2013325 (2019).","journal-title":"Nat. Rev. Cancer"},{"key":"10336_CR49","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/s41586-019-1922-8","volume":"577","author":"BA Helmink","year":"2020","unstructured":"Helmink, B. A. et al. B cells and tertiary lymphoid structures promote immunotherapy response. Nature 577, 549\u2013555 (2020).","journal-title":"Nature"},{"key":"10336_CR50","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1126\/science.aaa6204","volume":"348","author":"JA Joyce","year":"2015","unstructured":"Joyce, J. A. & Fearon, D. T. T cell exclusion, immune privilege, and the tumor microenvironment. Science 348, 74\u201380 (2015).","journal-title":"Science"},{"key":"10336_CR51","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/s41577-021-00539-6","volume":"21","author":"JD Chan","year":"2021","unstructured":"Chan, J. D. et al. Cellular networks controlling T cell persistence in adoptive cell therapy. Nat. Rev. Immunol. 21, 769\u2013784 (2021).","journal-title":"Nat. Rev. Immunol."},{"key":"10336_CR52","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/med.21293","volume":"34","author":"R Liu","year":"2014","unstructured":"Liu, R., Wang, X., Aihara, K. & Chen, L. Early diagnosis of complex diseases by molecular biomarkers, network biomarkers, and dynamical network biomarkers. Med. Res. Rev. 34, 455\u2013478 (2014).","journal-title":"Med. Res. Rev."},{"key":"10336_CR53","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/s41573-022-00413-7","volume":"21","author":"NA Maskalenko","year":"2022","unstructured":"Maskalenko, N. A., Zhigarev, D. & Campbell, K. S. Harnessing natural killer cells for cancer immunotherapy: dispatching the first responders. Nat. Rev. Drug Discov. 21, 559\u2013577 (2022).","journal-title":"Nat. Rev. Drug Discov."},{"key":"10336_CR54","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/s41577-022-00732-1","volume":"23","author":"NK Wolf","year":"2023","unstructured":"Wolf, N. K., Kissiov, D. U. & Raulet, D. H. Roles of natural killer cells in immunity to cancer, and applications to immunotherapy. Nat. Rev. Immunol. 23, 90\u2013105 (2023).","journal-title":"Nat. Rev. Immunol."},{"key":"10336_CR55","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1158\/2159-8290.CD-20-0655","volume":"11","author":"B C\u00f3zar","year":"2021","unstructured":"C\u00f3zar, B. et al. Tumor-infiltrating natural killer cells. Cancer Discov. 11, 34\u201344 (2021).","journal-title":"Cancer Discov."},{"key":"10336_CR56","doi-asserted-by":"crossref","unstructured":"Ali, A, et al. Natural killer cell immunosuppressive function requires CXCR3-dependent redistribution within lymphoid tissues. J. Clin. Investig. 131, e146686 (2021).","DOI":"10.1172\/JCI146686"},{"key":"10336_CR57","doi-asserted-by":"publisher","first-page":"2035","DOI":"10.1136\/gutjnl-2017-314098","volume":"67","author":"H Li","year":"2018","unstructured":"Li, H. et al. Regulatory NK cells mediated between immunosuppressive monocytes and dysfunctional T cells in chronic HBV infection. Gut 67, 2035\u20132044 (2018).","journal-title":"Gut"},{"key":"10336_CR58","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1158\/2159-8290.CD-15-0732","volume":"6","author":"D Gotthardt","year":"2016","unstructured":"Gotthardt, D. et al. STAT5 is a key regulator in NK cells and acts as a molecular switch from tumor surveillance to tumor promotion. Cancer Discov. 6, 414\u2013429 (2016).","journal-title":"Cancer Discov."},{"key":"10336_CR59","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1172\/JCI124635","volume":"130","author":"S McArthur","year":"2020","unstructured":"McArthur, S. et al. Annexin A1 drives macrophage skewing to accelerate muscle regeneration through AMPK activation. J. Clin. Investig. 130, 1156\u20131167 (2020).","journal-title":"J. Clin. Investig."},{"key":"10336_CR60","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/j.immuni.2018.03.030","volume":"48","author":"M Gamliel","year":"2018","unstructured":"Gamliel, M. et al. Trained memory of human uterine NK cells enhances their function in subsequent pregnancies. Immunity 48, 951\u2013962.e5 (2018).","journal-title":"Immunity"},{"key":"10336_CR61","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1038\/s41591-018-0157-9","volume":"24","author":"N Auslander","year":"2018","unstructured":"Auslander, N. et al. Robust prediction of response to immune checkpoint blockade therapy in metastatic melanoma. Nat. Med. 24, 1545\u20131549 (2018).","journal-title":"Nat. Med."},{"key":"10336_CR62","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1158\/2326-6066.CIR-19-0005","volume":"8","author":"AR Jaiswal","year":"2020","unstructured":"Jaiswal, A. R. et al. Melanoma evolves complete immunotherapy resistance through the acquisition of a hypermetabolic phenotype. Cancer Immunol. Res. 8, 1365\u20131380 (2020).","journal-title":"Cancer Immunol. Res."},{"key":"10336_CR63","doi-asserted-by":"crossref","unstructured":"Amato, C. M. et al. Pre-treatment mutational and transcriptomic landscape of responding metastatic melanoma patients to anti-PD1 immunotherapy. Cancers (Basel) 12, 1943 (2020).","DOI":"10.3390\/cancers12071943"},{"key":"10336_CR64","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1016\/j.cell.2017.09.028","volume":"171","author":"N Riaz","year":"2017","unstructured":"Riaz, N. et al. Tumor and microenvironment evolution during immunotherapy with nivolumab. Cell 171, 934\u2013949.e16 (2017).","journal-title":"Cell"},{"key":"10336_CR65","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1016\/j.cell.2020.09.015","volume":"183","author":"DK Wells","year":"2020","unstructured":"Wells, D. K. et al. Key parameters of tumor epitope immunogenicity revealed through a consortium approach improve neoantigen prediction. Cell 183, 818\u2013834.e13 (2020).","journal-title":"Cell"},{"key":"10336_CR66","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.cell.2016.02.065","volume":"165","author":"W Hugo","year":"2016","unstructured":"Hugo, W. et al. Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell 165, 35\u201344 (2016).","journal-title":"Cell"},{"key":"10336_CR67","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1038\/s41591-019-0499-y","volume":"25","author":"C Segovia","year":"2019","unstructured":"Segovia, C. et al. Inhibition of a G9a\/DNMT network triggers immune-mediated bladder cancer regression. Nat. Med. 25, 1073\u20131081 (2019).","journal-title":"Nat. Med."},{"key":"10336_CR68","doi-asserted-by":"publisher","first-page":"e1002309","DOI":"10.1371\/journal.pmed.1002309","volume":"14","author":"A Snyder","year":"2017","unstructured":"Snyder, A. et al. Contribution of systemic and somatic factors to clinical response and resistance to PD-L1 blockade in urothelial cancer: an exploratory multi-omic analysis. PLoS Med. 14, e1002309 (2017).","journal-title":"PLoS Med."},{"key":"10336_CR69","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1038\/nature25501","volume":"554","author":"S Mariathasan","year":"2018","unstructured":"Mariathasan, S. et al. TGF\u03b2 attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature 554, 544\u2013548 (2018).","journal-title":"Nature"},{"key":"10336_CR70","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1158\/2326-6066.CIR-16-0072","volume":"4","author":"ML Ascierto","year":"2016","unstructured":"Ascierto, M. L. et al. The intratumoral balance between metabolic and immunologic gene expression is associated with anti-PD-1 response in patients with renal cell carcinoma. Cancer Immunol. Res. 4, 726\u2013733 (2016).","journal-title":"Cancer Immunol. Res."},{"key":"10336_CR71","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1038\/s41591-020-1044-8","volume":"26","author":"RJ Motzer","year":"2020","unstructured":"Motzer, R. J. et al. Avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma: biomarker analysis of the phase 3 JAVELIN Renal 101 trial. Nat. Med. 26, 1733\u20131741 (2020).","journal-title":"Nat. Med."},{"key":"10336_CR72","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1038\/s41591-020-0839-y","volume":"26","author":"DA Braun","year":"2020","unstructured":"Braun, D. A. et al. Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma. Nat. Med. 26, 909\u2013918 (2020).","journal-title":"Nat. Med."},{"key":"10336_CR73","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1038\/s12276-020-00493-8","volume":"52","author":"JW Cho","year":"2020","unstructured":"Cho, J. W. et al. Genome-wide identification of differentially methylated promoters and enhancers associated with response to anti-PD-1 therapy in non-small cell lung cancer. Exp. Mol. Med. 52, 1550\u20131563 (2020).","journal-title":"Exp. Mol. Med."},{"key":"10336_CR74","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12159-9","volume":"10","author":"H Jung","year":"2019","unstructured":"Jung, H. et al. DNA methylation loss promotes immune evasion of tumours with high mutation and copy number load. Nat. Commun. 10, 4278 (2019).","journal-title":"Nat. Commun."},{"key":"10336_CR75","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/j.ccell.2021.05.009","volume":"39","author":"L Pusztai","year":"2021","unstructured":"Pusztai, L. et al. Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II\/III breast cancer: results from the adaptively randomized I-SPY2 trial. Cancer Cell 39, 989\u2013998.e5 (2021).","journal-title":"Cancer Cell"},{"key":"10336_CR76","doi-asserted-by":"publisher","first-page":"3351","DOI":"10.1158\/1078-0432.CCR-20-4443","volume":"27","author":"T van den Ende","year":"2021","unstructured":"van den Ende, T. et al. Neoadjuvant chemoradiotherapy combined with atezolizumab for resectable esophageal adenocarcinoma: a single-arm Phase II Feasibility Trial (PERFECT). Clin. Cancer Res. 27, 3351\u20133359 (2021).","journal-title":"Clin. Cancer Res."},{"key":"10336_CR77","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1038\/s43018-021-00269-7","volume":"2","author":"AR Parikh","year":"2021","unstructured":"Parikh, A. R. et al. Radiation therapy enhances immunotherapy response in microsatellite stable colorectal and pancreatic adenocarcinoma in a phase II trial. Nat. Cancer 2, 1124\u20131135 (2021).","journal-title":"Nat. Cancer"},{"key":"10336_CR78","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","volume":"45","author":"EA Eisenhauer","year":"2009","unstructured":"Eisenhauer, E. A. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer 45, 228\u2013247 (2009).","journal-title":"Eur. J. Cancer"},{"key":"10336_CR79","unstructured":"Prada, C., Lima, D. & Nakaya, H. MetaVolcanoR: gene expression meta-analysis visualization tool. R Package Version 1.0 (2020)."},{"key":"10336_CR80","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/j.immuni.2018.03.023","volume":"48","author":"V Thorsson","year":"2018","unstructured":"Thorsson, V. et al. The immune landscape of cancer. Immunity 48, 812\u2013830.e14 (2018).","journal-title":"Immunity"},{"key":"10336_CR81","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/nature11252","volume":"487","author":"Cancer Genome Atlas Network","year":"2012","unstructured":"Cancer Genome Atlas Network Comprehensive molecular characterization of human colon and rectal cancer. Nature 487, 330\u2013337 (2012).","journal-title":"Nature"},{"key":"10336_CR82","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1038\/nm.4191","volume":"22","author":"RJ Hause","year":"2016","unstructured":"Hause, R. J., Pritchard, C. C., Shendure, J. & Salipante, S. J. Classification and characterization of microsatellite instability across 18 cancer types. Nat. Med. 22, 1342\u20131350 (2016).","journal-title":"Nat. Med."},{"key":"10336_CR83","doi-asserted-by":"crossref","unstructured":"Peschel, S., M\u00fcller, C. L., von Mutiusy, E., Boulesteix, A.L. & Depner, M. NetCoMi: network construction and comparison for microbiome data in R. Brief Bioinform. 22, bbaa290 (2021).","DOI":"10.1093\/bib\/bbaa290"},{"key":"10336_CR84","doi-asserted-by":"publisher","first-page":"2713","DOI":"10.1093\/bioinformatics\/btw187","volume":"32","author":"IH Goenawan","year":"2016","unstructured":"Goenawan, I. H., Bryan, K. & Lynn, D. J. DyNet: visualization and analysis of dynamic molecular interaction networks. Bioinformatics 32, 2713\u20132715 (2016).","journal-title":"Bioinformatics"},{"key":"10336_CR85","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498\u20132504 (2003).","journal-title":"Genome Res."},{"key":"10336_CR86","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1016\/j.ccell.2023.04.011","volume":"41","author":"J Li","year":"2023","unstructured":"Li, J. et al. Remodeling of the immune and stromal cell compartment by PD-1 blockade in mismatch repair-deficient colorectal cancer. Cancer Cell 41, 1152\u20131169.e7 (2023).","journal-title":"Cancer Cell"},{"key":"10336_CR87","doi-asserted-by":"publisher","first-page":"2094","DOI":"10.1158\/1078-0432.CCR-21-3570","volume":"28","author":"A Obradovic","year":"2022","unstructured":"Obradovic, A. et al. Immunostimulatory cancer-associated fibroblast subpopulations can predict immunotherapy response in head and neck cancer. Clin. Cancer Res. 28, 2094\u20132109 (2022).","journal-title":"Clin. Cancer Res."},{"key":"10336_CR88","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1038\/s41591-019-0522-3","volume":"25","author":"KE Yost","year":"2019","unstructured":"Yost, K. E. et al. Clonal replacement of tumor-specific T cells following PD-1 blockade. Nat. Med. 25, 1251\u20131259 (2019).","journal-title":"Nat. Med."},{"key":"10336_CR89","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","volume":"184","author":"Y Hao","year":"2021","unstructured":"Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573\u20133587.e29 (2021).","journal-title":"Cell"},{"key":"10336_CR90","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.20073469","author":"Y Xie","year":"2026","unstructured":"Xie, Y. CIsAtlas: a cellular atlas of immunotherapy. Zenodo https:\/\/doi.org\/10.5281\/zenodo.20073469 (2026).","journal-title":"Zenodo"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10336-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10336-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10336-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T11:02:04Z","timestamp":1787050924000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10336-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,26]]},"references-count":90,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["10336"],"URL":"https:\/\/doi.org\/10.1038\/s42003-026-10336-3","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,26]]},"assertion":[{"value":"1 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"1114"}}