{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:57:36Z","timestamp":1793833056775,"version":"4.6.1"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"QDFY Research Foundation","award":["QDFYQN2024211"],"award-info":[{"award-number":["QDFYQN2024211"]}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["ZR2025QC1933Z"],"award-info":[{"award-number":["ZR2025QC1933Z"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100020206","name":"Health Commission of Shandong Province","doi-asserted-by":"crossref","award":["202504080911"],"award-info":[{"award-number":["202504080911"]}],"id":[{"id":"10.13039\/501100020206","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172744"],"award-info":[{"award-number":["82172744"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["21Y11913700"],"award-info":[{"award-number":["21Y11913700"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Hematol Oncol"],"DOI":"10.1186\/s40164-026-00748-6","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T03:17:21Z","timestamp":1771989441000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tertiary lymphoid structures correlate with reduced recurrence risk and enhanced antitumor immunity in esophageal squamous cell carcinoma with pathologic non-complete response to neoadjuvant chemoimmunotherapy"],"prefix":"10.1186","volume":"15","author":[{"given":"Yang","family":"Wo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongfei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhou","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuxia","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihua","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"issue":"8","key":"748_CR1","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1001\/jamasurg.2021.2373","volume":"156","author":"H Yang","year":"2021","unstructured":"Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, et al. Long-term efficacy of neoadjuvant chemoradiotherapy plus surgery for the treatment of locally advanced esophageal squamous cell carcinoma: the NEOCRTEC5010 randomized clinical trial. JAMA Surg. 2021;156(8):721\u20139.","journal-title":"JAMA Surg"},{"issue":"18","key":"748_CR2","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.1200\/JCO.20.03614","volume":"39","author":"BM Eyck","year":"2021","unstructured":"Eyck BM, van Lanschot JJB, Hulshof M, van der Wilk BJ, Shapiro J, van Hagen P, et al. Ten-year outcome of neoadjuvant chemoradiotherapy plus surgery for esophageal cancer: the randomized controlled cross trial. J Clin Oncol. 2021;39(18):1995\u20132004.","journal-title":"J Clin Oncol"},{"issue":"5","key":"748_CR3","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1056\/NEJMoa2111380","volume":"386","author":"Y Doki","year":"2022","unstructured":"Doki Y, Ajani JA, Kato K, Xu J, Wyrwicz L, Motoyama S, et al. Nivolumab combination therapy in advanced esophageal squamous-cell carcinoma. N Engl J Med. 2022;386(5):449\u201362.","journal-title":"N Engl J Med"},{"issue":"11","key":"748_CR4","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.39778","volume":"5","author":"F Ge","year":"2022","unstructured":"Ge F, Huo Z, Cai X, Hu Q, Chen W, Lin G, et al. Evaluation of clinical and safety outcomes of neoadjuvant immunotherapy combined with chemotherapy for patients with resectable esophageal cancer: a systematic review and meta-analysis. JAMA Netw Open. 2022;5(11):e2239778.","journal-title":"JAMA Netw Open"},{"issue":"6","key":"748_CR5","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1016\/j.jtcvs.2009.07.069","volume":"138","author":"RA Meguid","year":"2009","unstructured":"Meguid RA, Hooker CM, Taylor JT, Kleinberg LR, Cattaneo SM 2nd, Sussman MS, et al. Recurrence after neoadjuvant chemoradiation and surgery for esophageal cancer: does the pattern of recurrence differ for patients with complete response and those with partial or no response? J Thorac Cardiovasc Surg. 2009;138(6):1309\u201317.","journal-title":"J Thorac Cardiovasc Surg"},{"key":"748_CR6","doi-asserted-by":"crossref","unstructured":"Donahue JM, Nichols FC, Li Z, Schomas DA, Allen MS, Cassivi SD, et al. Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal cancer is associated with enhanced survival. Ann Thorac Surg. 2009;87(2):392\u20138; discussion 8\u20139.","DOI":"10.1016\/j.athoracsur.2008.11.001"},{"key":"748_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112558","volume":"138","author":"Y Guo","year":"2024","unstructured":"Guo Y, Xu X, Wang T, Liu Y, Gu D, Fang Y, et al. Efficacy, safety, and survival of neoadjuvant immunotherapy plus chemotherapy in locally advanced esophageal squamous cell carcinoma: a real-world retrospective study. Int Immunopharmacol. 2024;138:112558.","journal-title":"Int Immunopharmacol"},{"issue":"2","key":"748_CR8","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.jtcvs.2023.12.030","volume":"168","author":"YK Yu","year":"2024","unstructured":"Yu YK, Meng FY, Wei XF, Chen XK, Li HM, Liu Q, et al. Neoadjuvant chemotherapy combined with immunotherapy versus neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. J Thorac Cardiovasc Surg. 2024;168(2):417\u201328.","journal-title":"J Thorac Cardiovasc Surg."},{"issue":"5","key":"748_CR9","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-025-03988-3","volume":"74","author":"A Liu","year":"2025","unstructured":"Liu A, Liu D, Liu X, Chi Y, Guo L, Li D, et al. The prognosis prediction value of CD69+ CD8+ tissue-resident memory T cell as a novel indicator of pathologic complete response heterogeneity following different neoadjuvant therapy regimen in esophageal squamous cell carcinoma. Cancer Immunol Immunother. 2025;74(5):147.","journal-title":"Cancer Immunol Immunother"},{"issue":"3","key":"748_CR10","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1245\/s10434-022-12752-1","volume":"30","author":"J Xu","year":"2023","unstructured":"Xu J, Yan C, Li Z, Cao Y, Duan H, Ke S. Efficacy and safety of neoadjuvant chemoimmunotherapy in resectable esophageal squamous cell carcinoma: a meta-analysis. Ann Surg Oncol. 2023;30(3):1597\u2013613.","journal-title":"Ann Surg Oncol"},{"issue":"10","key":"748_CR11","doi-asserted-by":"publisher","first-page":"2254","DOI":"10.1016\/j.immuni.2023.08.009","volume":"56","author":"WH Fridman","year":"2023","unstructured":"Fridman WH, Meylan M, Pupier G, Calvez A, Hernandez I, Sautes-Fridman C. Tertiary lymphoid structures and B cells: an intratumoral immunity cycle. Immunity. 2023;56(10):2254\u201369.","journal-title":"Immunity"},{"issue":"1","key":"748_CR12","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s40164-025-00695-8","volume":"14","author":"M Radandish","year":"2025","unstructured":"Radandish M, Mashhadi N, Aghayan AH, Taghizadeh M, Salehianfard S, Yahyazadeh S, et al. In-depth insight into tumor-infiltrating stromal cells linked to tertiary lymphoid structures and their prospective function in cancer immunotherapy. Exp Hematol Oncol. 2025;14(1):105.","journal-title":"Exp Hematol Oncol"},{"issue":"1","key":"748_CR13","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-025-01754-7","volume":"18","author":"S Deng","year":"2025","unstructured":"Deng S, Chen Y, Song B, Wang H, Huang S, Wu K, et al. Tertiary lymphoid structures in cancer: spatiotemporal heterogeneity, immune orchestration, and translational opportunities\u200b\u200b. J Hematol Oncol. 2025;18(1):97.","journal-title":"J Hematol Oncol"},{"issue":"7","key":"748_CR14","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1586\/17474124.2014.913478","volume":"8","author":"KE O'Sullivan","year":"2014","unstructured":"O\u2019Sullivan KE, Phelan JJ, O\u2019Hanlon C, Lysaght J, O\u2019Sullivan JN, Reynolds JV. The role of inflammation in cancer of the esophagus. Expert Rev Gastroenterol Hepatol. 2014;8(7):749\u201360.","journal-title":"Expert Rev Gastroenterol Hepatol"},{"issue":"9","key":"748_CR15","doi-asserted-by":"publisher","first-page":"3132","DOI":"10.1111\/cas.14541","volume":"111","author":"Y Baba","year":"2020","unstructured":"Baba Y, Nomoto D, Okadome K, Ishimoto T, Iwatsuki M, Miyamoto Y, et al. Tumor immune microenvironment and immune checkpoint inhibitors in esophageal squamous cell carcinoma. Cancer Sci. 2020;111(9):3132\u201341.","journal-title":"Cancer Sci"},{"issue":"4","key":"748_CR16","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/s41416-021-01331-y","volume":"125","author":"M Davern","year":"2021","unstructured":"Davern M, Donlon NE, Power R, Hayes C, King R, Dunne MR, et al. The tumour immune microenvironment in oesophageal cancer. Br J Cancer. 2021;125(4):479\u201394.","journal-title":"Br J Cancer"},{"issue":"3","key":"748_CR17","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1016\/j.jhep.2021.10.030","volume":"76","author":"D Guang-Yu","year":"2022","unstructured":"Guang-Yu D, Jia-Qiang M, Jing-Ping Y, Chen X, Ling Y, Zhang S, et al. Distribution and density of tertiary lymphoid structures predict clinical outcome in intrahepatic cholangiocarcinoma. J Hepatol. 2022;76(3):608\u201318.","journal-title":"J Hepatol"},{"issue":"1","key":"748_CR18","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.jhep.2018.09.003","volume":"70","author":"J Calderaro","year":"2019","unstructured":"Calderaro J, Petitprez F, Becht E, Laurent A, Hirsch TZ, Rousseau B, et al. Intra-tumoral tertiary lymphoid structures are associated with a low risk of early recurrence of hepatocellular carcinoma. J Hepatol. 2019;70(1):58\u201365.","journal-title":"J Hepatol"},{"issue":"1","key":"748_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35238-w","volume":"14","author":"S Tietscher","year":"2023","unstructured":"Tietscher S, Wagner J, Anzeneder T, Langwieder C, Rees M, Sobottka B, et al. A comprehensive single-cell map of T cell exhaustion-associated immune environments in human breast cancer. Nat Commun. 2023;14(1):98.","journal-title":"Nat Commun"},{"issue":"16","key":"748_CR20","doi-asserted-by":"publisher","first-page":"4381","DOI":"10.1158\/1078-0432.CCR-19-2929","volume":"26","author":"M Meylan","year":"2020","unstructured":"Meylan M, Petitprez F, Lacroix L, Di Tommaso L, Roncalli M, Bougouin A, et al. Early Hepatic Lesions Display Immature Tertiary Lymphoid Structures and Show Elevated Expression of Immune Inhibitory and Immunosuppressive Molecules. Clin Cancer Res. 2020;26(16):4381\u20139.","journal-title":"Clin Cancer Res"},{"issue":"12","key":"748_CR21","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1038\/s41416-023-02235-9","volume":"128","author":"Y Hayashi","year":"2023","unstructured":"Hayashi Y, Makino T, Sato E, Ohshima K, Nogi Y, Kanemura T, et al. Density and maturity of peritumoral tertiary lymphoid structures in oesophageal squamous cell carcinoma predicts patient survival and response to immune checkpoint inhibitors. Br J Cancer. 2023;128(12):2175\u201385.","journal-title":"Br J Cancer"},{"issue":"3","key":"748_CR22","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1016\/j.jtcvs.2023.08.056","volume":"167","author":"Y Yang","year":"2024","unstructured":"Yang Y, Liu J, Liu Z, Zhu L, Chen H, Yu B, et al. Two-year outcomes of clinical N2\u20133 esophageal squamous cell carcinoma after neoadjuvant chemotherapy and immunotherapy from the phase 2 NICE study. J Thorac Cardiovasc Surg. 2024;167(3):838\u201347.","journal-title":"J Thorac Cardiovasc Surg."},{"issue":"5","key":"748_CR23","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1200\/JCO.2013.51.2186","volume":"32","author":"V Oppedijk","year":"2014","unstructured":"Oppedijk V, van der Gaast A, van Lanschot JJ, van Hagen P, van Os R, van Rij CM, et al. Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J Clin Oncol. 2014;32(5):385\u201391.","journal-title":"J Clin Oncol"},{"issue":"4","key":"748_CR24","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.cels.2019.03.003","volume":"8","author":"CS McGinnis","year":"2019","unstructured":"McGinnis CS, Murrow LM, Gartner ZJ. DoubletFinder: doublet detection in single-cell RNA sequencing data using artificial nearest neighbors. Cell Syst. 2019;8(4):329-37 e4.","journal-title":"Cell Syst"},{"issue":"5","key":"748_CR25","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012;16(5):284\u20137.","journal-title":"OMICS"},{"key":"748_CR26","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.22139.1","volume":"9","author":"N Borcherding","year":"2020","unstructured":"Borcherding N, Bormann NL, Kraus G. scRepertoire: an R-based toolkit for single-cell immune receptor analysis. F1000Res. 2020;9:47.","journal-title":"F1000Res"},{"issue":"6476","key":"748_CR27","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1126\/science.aax0249","volume":"367","author":"GS Gulati","year":"2020","unstructured":"Gulati GS, Sikandar SS, Wesche DJ, Manjunath A, Bharadwaj A, Berger MJ, et al. Single-cell transcriptional diversity is a hallmark of developmental potential. Science. 2020;367(6476):405\u201311.","journal-title":"Science"},{"issue":"1","key":"748_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9","volume":"12","author":"S Jin","year":"2021","unstructured":"Jin S, Guerrero-Juarez CF, Zhang L, Chang I, Ramos R, Kuan CH, et al. Inference and analysis of cell-cell communication using CellChat. Nat Commun. 2021;12(1):1088.","journal-title":"Nat Commun"},{"issue":"2","key":"748_CR29","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/s41592-019-0667-5","volume":"17","author":"R Browaeys","year":"2020","unstructured":"Browaeys R, Saelens W, Saeys Y. NicheNet: modeling intercellular communication by linking ligands to target genes. Nat Methods. 2020;17(2):159\u201362.","journal-title":"Nat Methods"},{"issue":"3","key":"748_CR30","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1016\/j.cell.2018.09.018","volume":"175","author":"M Angelova","year":"2018","unstructured":"Angelova M, Mlecnik B, Vasaturo A, Bindea G, Fredriksen T, Lafontaine L, et al. Evolution of metastases in space and time under immune selection. Cell. 2018;175(3):751\u201365.","journal-title":"Cell."},{"issue":"7735","key":"748_CR31","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1038\/s41586-018-0694-x","volume":"564","author":"L Zhang","year":"2018","unstructured":"Zhang L, Yu X, Zheng L, Zhang Y, Li Y, Fang Q, et al. Lineage tracking reveals dynamic relationships of T cells in colorectal cancer. Nature. 2018;564(7735):268\u201372.","journal-title":"Nature"},{"issue":"7791","key":"748_CR32","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/s41586-019-1922-8","volume":"577","author":"BA Helmink","year":"2020","unstructured":"Helmink BA, Reddy SM, Gao J, Zhang S, Basar R, Thakur R, et al. B cells and tertiary lymphoid structures promote immunotherapy response. Nature. 2020;577(7791):549.","journal-title":"Nature"},{"issue":"11","key":"748_CR33","doi-asserted-by":"publisher","first-page":"2626","DOI":"10.1158\/2159-8290.CD-21-1658","volume":"12","author":"D Hao","year":"2022","unstructured":"Hao D, Han G, Sinjab A, Gomez-Bolanos LI, Lazcano R, Serrano A, et al. The single-cell immunogenomic landscape of B and plasma cells in early-stage lung adenocarcinoma. Cancer Discov. 2022;12(11):2626\u201345.","journal-title":"Cancer Discov"},{"issue":"5","key":"748_CR34","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1038\/s41577-019-0257-x","volume":"20","author":"GV Sharonov","year":"2020","unstructured":"Sharonov GV, Serebrovskaya EO, Yuzhakova DV, Britanova OV, Chudakov DM. B cells, plasma cells and antibody repertoires in the tumour microenvironment. Nat Rev Immunol. 2020;20(5):294\u2013307.","journal-title":"Nat Rev Immunol"},{"issue":"Suppl","key":"748_CR35","doi-asserted-by":"publisher","first-page":"S35","DOI":"10.1016\/S0092-8674(02)00706-7","volume":"109","author":"FN Papavasiliou","year":"2002","unstructured":"Papavasiliou FN, Schatz DG. Somatic hypermutation of immunoglobulin genes: merging mechanisms for genetic diversity. Cell. 2002;109(Suppl):S35-44.","journal-title":"Cell"},{"issue":"3","key":"748_CR36","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.ccell.2022.02.002","volume":"40","author":"NS Patil","year":"2022","unstructured":"Patil NS, Nabet BY, Muller S, Koeppen H, Zou W, Giltnane J, et al. Intratumoral plasma cells predict outcomes to PD-L1 blockade in non-small cell lung cancer. Cancer Cell. 2022;40(3):289-300 e4.","journal-title":"Cancer Cell"},{"issue":"10","key":"748_CR37","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/nri1886","volume":"6","author":"A Radbruch","year":"2006","unstructured":"Radbruch A, Muehlinghaus G, Luger EO, Inamine A, Smith KG, Dorner T, et al. Competence and competition: the challenge of becoming a long-lived plasma cell. Nat Rev Immunol. 2006;6(10):741\u201350.","journal-title":"Nat Rev Immunol"},{"issue":"11","key":"748_CR38","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1038\/s41590-022-01345-5","volume":"23","author":"X Liu","year":"2022","unstructured":"Liu X, Yao J, Zhao Y, Wang J, Qi H. Heterogeneous plasma cells and long-lived subsets in response to immunization, autoantigen and microbiota. Nat Immunol. 2022;23(11):1564\u201376.","journal-title":"Nat Immunol"},{"issue":"6","key":"748_CR39","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1038\/s41591-023-02371-y","volume":"29","author":"Y Chu","year":"2023","unstructured":"Chu Y, Dai E, Li Y, Han G, Pei G, Ingram DR, et al. Pan-cancer T cell atlas links a cellular stress response state to immunotherapy resistance. Nat Med. 2023;29(6):1550\u201362.","journal-title":"Nat Med"},{"issue":"6574","key":"748_CR40","doi-asserted-by":"publisher","first-page":"6474","DOI":"10.1126\/science.abe6474","volume":"374","author":"L Zheng","year":"2021","unstructured":"Zheng L, Qin S, Si W, Wang A, Xing B, Gao R, et al. Pan-cancer single-cell landscape of tumor-infiltrating T cells. Science. 2021;374(6574):6474.","journal-title":"Science."},{"issue":"4","key":"748_CR41","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1038\/s43587-022-00198-9","volume":"2","author":"OJ Luo","year":"2022","unstructured":"Luo OJ, Lei W, Zhu G, Ren Z, Xu Y, Xiao C, et al. Multidimensional single-cell analysis of human peripheral blood reveals characteristic features of the immune system landscape in aging and frailty. Nat Aging. 2022;2(4):348\u201364.","journal-title":"Nat Aging"},{"issue":"6","key":"748_CR42","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/nri3667","volume":"14","author":"L Klein","year":"2014","unstructured":"Klein L, Kyewski B, Allen PM, Hogquist KA. Positive and negative selection of the T cell repertoire: what thymocytes see (and don\u2019t see). Nat Rev Immunol. 2014;14(6):377\u201391.","journal-title":"Nat Rev Immunol"},{"issue":"7706","key":"748_CR43","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/s41586-018-0130-2","volume":"557","author":"Y Simoni","year":"2018","unstructured":"Simoni Y, Becht E, Fehlings M, Loh CY, Koo SL, Teng KWW, et al. Bystander CD8(+) t cells are abundant and phenotypically distinct in human tumour infiltrates. Nature. 2018;557(7706):575\u20139.","journal-title":"Nature"},{"issue":"7870","key":"748_CR44","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/s41586-021-03704-y","volume":"596","author":"G Oliveira","year":"2021","unstructured":"Oliveira G, Stromhaug K, Klaeger S, Kula T, Frederick DT, Le PM, et al. Phenotype, specificity and avidity of antitumour CD8(+) T cells in melanoma. Nature. 2021;596(7870):119\u201325.","journal-title":"Nature"},{"issue":"1","key":"748_CR45","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/s43018-021-00292-8","volume":"3","author":"B Liu","year":"2022","unstructured":"Liu B, Hu X, Feng K, Gao R, Xue Z, Zhang S, et al. Temporal single-cell tracing reveals clonal revival and expansion of precursor exhausted T cells during anti-PD-1 therapy in lung cancer. Nat Cancer. 2022;3(1):108\u201321.","journal-title":"Nat Cancer"},{"issue":"9","key":"748_CR46","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1038\/s43018-022-00433-7","volume":"3","author":"B Liu","year":"2022","unstructured":"Liu B, Zhang Y, Wang D, Hu X, Zhang Z. Single-cell meta-analyses reveal responses of tumor-reactive CXCL13(+) T cells to immune-checkpoint blockade. Nat Cancer. 2022;3(9):1123\u201336.","journal-title":"Nat Cancer"},{"issue":"3","key":"748_CR47","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.ccell.2023.02.014","volume":"41","author":"C Tay","year":"2023","unstructured":"Tay C, Tanaka A, Sakaguchi S. Tumor-infiltrating regulatory T cells as targets of cancer immunotherapy. Cancer Cell. 2023;41(3):450\u201365.","journal-title":"Cancer Cell"},{"issue":"1","key":"748_CR48","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1093\/intimm\/dxad041","volume":"36","author":"H Yoshitomi","year":"2024","unstructured":"Yoshitomi H. Peripheral helper T cells, mavericks of peripheral immune responses. Int Immunol. 2024;36(1):9\u201316.","journal-title":"Int Immunol"},{"issue":"3","key":"748_CR49","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/s43018-022-00338-5","volume":"3","author":"M Cohen","year":"2022","unstructured":"Cohen M, Giladi A, Barboy O, Hamon P, Li B, Zada M, et al. The interaction of CD4(+) helper T cells with dendritic cells shapes the tumor microenvironment and immune checkpoint blockade response. Nat Cancer. 2022;3(3):303\u201317.","journal-title":"Nat Cancer"},{"key":"748_CR50","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.157215","author":"M Ukita","year":"2022","unstructured":"Ukita M, Hamanishi J, Yoshitomi H, Yamanoi K, Takamatsu S, Ueda A, et al. CXCL13-producing CD4+ T cells accumulate in the early phase of tertiary lymphoid structures in ovarian cancer. JCI Insight. 2022. https:\/\/doi.org\/10.1172\/jci.insight.157215.","journal-title":"JCI Insight"},{"issue":"3","key":"748_CR51","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1016\/j.cell.2021.01.010","volume":"184","author":"S Cheng","year":"2021","unstructured":"Cheng S, Li Z, Gao R, Xing B, Gao Y, Yang Y, et al. A pan-cancer single-cell transcriptional atlas of tumor infiltrating myeloid cells. Cell. 2021;184(3):792-809 e23.","journal-title":"Cell"},{"issue":"2","key":"748_CR52","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1111\/joim.12019","volume":"273","author":"L Claesson-Welsh","year":"2013","unstructured":"Claesson-Welsh L, Welsh M. Vegfa and tumour angiogenesis. J Intern Med. 2013;273(2):114\u201327.","journal-title":"J Intern Med"},{"issue":"3","key":"748_CR53","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0391-6","volume":"9","author":"H Zhao","year":"2018","unstructured":"Zhao H, Chen Q, Alam A, Cui J, Suen KC, Soo AP, et al. The role of osteopontin in the progression of solid organ tumour. Cell Death Dis. 2018;9(3):356.","journal-title":"Cell Death Dis"},{"issue":"6","key":"748_CR54","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1038\/s41571-022-00620-6","volume":"19","author":"MJ Pittet","year":"2022","unstructured":"Pittet MJ, Michielin O, Migliorini D. Clinical relevance of tumour-associated macrophages. Nat Rev Clin Oncol. 2022;19(6):402\u201321.","journal-title":"Nat Rev Clin Oncol"},{"issue":"12","key":"748_CR55","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.1016\/j.ccell.2024.11.002","volume":"42","author":"P Schol","year":"2024","unstructured":"Schol P, van Elsas MJ, Middelburg J, Nijen Twilhaar MK, van Hall T, van der Sluis TC, et al. Myeloid effector cells in cancer. Cancer Cell. 2024;42(12):1997\u20132014.","journal-title":"Cancer Cell"},{"issue":"7786","key":"748_CR56","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41586-019-1805-z","volume":"576","author":"RC Lynn","year":"2019","unstructured":"Lynn RC, Weber EW, Sotillo E, Gennert D, Xu P, Good Z, et al. c-Jun overexpression in CAR T cells induces exhaustion resistance. Nature. 2019;576(7786):293\u2013300.","journal-title":"Nature"},{"key":"748_CR57","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2023.102397","volume":"85","author":"D Schnoegl","year":"2023","unstructured":"Schnoegl D, Hiesinger A, Huntington ND, Gotthardt D. AP-1 transcription factors in cytotoxic lymphocyte development and antitumor immunity. Curr Opin Immunol. 2023;85:102397.","journal-title":"Curr Opin Immunol"},{"issue":"11","key":"748_CR58","doi-asserted-by":"publisher","first-page":"3010","DOI":"10.1002\/eji.200839154","volume":"39","author":"S Ju","year":"2009","unstructured":"Ju S, Zhu Y, Liu L, Dai S, Li C, Chen E, et al. Gadd45b and Gadd45g are important for anti-tumor immune responses. Eur J Immunol. 2009;39(11):3010\u20138.","journal-title":"Eur J Immunol"},{"issue":"1","key":"748_CR59","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21099-2","volume":"12","author":"R Yang","year":"2021","unstructured":"Yang R, Sun L, Li CF, Wang YH, Yao J, Li H, et al. Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy. Nat Commun. 2021;12(1):832.","journal-title":"Nat Commun"},{"issue":"1","key":"748_CR60","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/s40164-024-00587-3","volume":"13","author":"K Chen","year":"2024","unstructured":"Chen K, Li Y, Ni J, Yang X, Zhou Y, Pang Y, et al. Identification of a novel subtype of SPP1 + macrophages expressing SIRPalpha: implications for tumor immune evasion and treatment response prediction. Exp Hematol Oncol. 2024;13(1):119.","journal-title":"Exp Hematol Oncol"},{"issue":"1","key":"748_CR61","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-024-00543-1","volume":"13","author":"S Zheng","year":"2024","unstructured":"Zheng S, Wang W, Shen L, Yao Y, Xia W, Ni C. Tumor battlefield within inflamed, excluded or desert immune phenotypes: the mechanisms and strategies. Exp Hematol Oncol. 2024;13(1):80.","journal-title":"Exp Hematol Oncol"},{"key":"748_CR62","doi-asserted-by":"publisher","DOI":"10.1038\/srep01365","volume":"3","author":"V Zinchuk","year":"2013","unstructured":"Zinchuk V, Wu Y, Grossenbacher-Zinchuk O. Bridging the gap between qualitative and quantitative colocalization results in fluorescence microscopy studies. Sci Rep. 2013;3:1365.","journal-title":"Sci Rep"},{"issue":"8","key":"748_CR63","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1158\/0008-5472.CAN-23-3325","volume":"84","author":"G Petroni","year":"2024","unstructured":"Petroni G, Pillozzi S, Antonuzzo L. Exploiting tertiary lymphoid structures to stimulate antitumor immunity and improve immunotherapy efficacy. Cancer Res. 2024;84(8):1199\u2013209.","journal-title":"Cancer Res"}],"container-title":["Experimental Hematology & Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40164-026-00748-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40164-026-00748-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40164-026-00748-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:03:18Z","timestamp":1772118198000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40164-026-00748-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["748"],"URL":"https:\/\/doi.org\/10.1186\/s40164-026-00748-6","relation":{},"ISSN":["2162-3619"],"issn-type":[{"value":"2162-3619","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]},"assertion":[{"value":"8 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the institutional review board (IRB #20875697P). Written informed consent to participate was obtained from all patients.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors have agreed with publishing this manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"29"}}