Morgan E, Soerjomataram I, Rumgay H, Coleman HG, Thrift AP, Vignat J, et al. The Global Landscape of Esophageal Squamous Cell Carcinoma and Esophageal Adenocarcinoma Incidence and Mortality in 2020 and projections to 2040: new estimates from GLOBOCAN 2020. Gastroenterology. 2022;163:649–58.e2.
Google Scholar
van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge, Henegouwen MI, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–84.
Google Scholar
Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, et al. Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): a phase III multicenter, randomized, open-label clinical trial. J Clin Oncol. 2018;36:2796–803.
Google Scholar
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;39:1995–2004.
Google Scholar
Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359:1350–5.
Google Scholar
Kojima T, Shah MA, Muro K, Francois E, Adenis A, Hsu CH, et al. Randomized phase III KEYNOTE-181 study of pembrolizumab versus chemotherapy in advanced esophageal cancer. J Clin Oncol. 2020;38:4138–48.
Google Scholar
Kato K, Cho BC, Takahashi M, Okada M, Lin CY, Chin K, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20:1506–17.
Google Scholar
Huang J, Xu J, Chen Y, Zhuang W, Zhang Y, Chen Z, et al. Camrelizumab versus investigator’s choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2020;21:832–42.
Google Scholar
Shen L, Kato K, Kim SB, Ajani JA, Zhao K, He Z, et al. Tislelizumab versus chemotherapy as second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (RATIONALE-302): a randomized phase III study. J Clin Oncol. 2022;40:3065–76.
Google Scholar
Kuo HY, Guo JC, Hsu CH. Anti-PD-1 immunotherapy in advanced esophageal squamous cell carcinoma: A long-awaited breakthrough finally arrives. J Formos Med Assoc. 2020;119:565–8.
Google Scholar
Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021;398:759–71.
Google Scholar
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;386:449–62.
Google Scholar
Luo H, Lu J, Bai Y, Mao T, Wang J, Fan Q, et al. Effect of camrelizumab vs placebo added to chemotherapy on survival and progression-free survival in patients with advanced or metastatic esophageal squamous cell carcinoma: the ESCORT-1st randomized clinical trial. JAMA. 2021;326:916–25.
Google Scholar
Lu Z, Wang J, Shu Y, Liu L, Kong L, Yang L, et al. Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (ORIENT-15): multicentre, randomised, double blind, phase 3 trial. BMJ. 2022;377:e068714.
Google Scholar
Wang ZX, Cui C, Yao J, Zhang Y, Li M, Feng J, et al. Toripalimab plus chemotherapy in treatment-naive, advanced esophageal squamous cell carcinoma (JUPITER-06): a multi-center phase 3 trial. Cancer Cell. 2022;40:277–88.e3.
Google Scholar
Xu J, Kato K, Raymond E, Hubner RA, Shu Y, Pan Y, et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (RATIONALE-306): a global, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2023;24:483–95.
Google Scholar
Song Y, Zhang B, Xin D, Kou X, Tan Z, Zhang S, et al. First-line serplulimab or placebo plus chemotherapy in PD-L1-positive esophageal squamous cell carcinoma: a randomized, double-blind phase 3 trial. Nat Med. 2023;29:473–82.
Google Scholar
Kuo HY, Guo JC, Hsu CH. Embracing anti-PD-1 immunotherapy in the treatment of esophageal cancer: Implications of positive phase III trials in advanced and resected esophageal cancer. J Formos Med Assoc. 2023;122:4–8.
Google Scholar
Kelly RJ, Ajani JA, Kuzdzal J, Zander T, Van Cutsem E, Piessen G, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med. 2021;384:1191–203.
Google Scholar
Liu J, Blake SJ, Yong MC, Harjunpaa H, Ngiow SF, Takeda K, et al. Improved efficacy of neoadjuvant compared to adjuvant immunotherapy to eradicate metastatic disease. Cancer Discov. 2016;6:1382–99.
Google Scholar
Li F, Chen Y, Wu J, Li C, Chen S, Zhu Z, et al. The earlier, the better? A review of neoadjuvant immunotherapy in resectable non-small-cell lung cancer. Chronic Dis Transl Med. 2022;8:100–11.
Google Scholar
Bai R, Li L, Chen X, Chen N, Song W, Cui J. Neoadjuvant and adjuvant immunotherapy: opening new horizons for patients with early-stage non-small cell lung cancer. Front Oncol. 2020;10:575472.
Google Scholar
Patel SP, Othus M, Chen Y, Wright GP Jr., Yost KJ, Hyngstrom JR, et al. Neoadjuvant-adjuvant or adjuvant-only pembrolizumab in advanced melanoma. N Engl J Med. 2023;388:813–23.
Google Scholar
Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. 2022;386:1973–85.
Google Scholar
Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, et al. Perioperative pembrolizumab for early-stage non-small-cell lung cancer. N Engl J Med. 2023;389:491–503.
Google Scholar
Guo JC, Huang TC, Lin CC, Hsieh MS, Chang CH, Huang PM, et al. Postchemoradiotherapy pathologic stage classified by the American Joint Committee on the cancer staging system predicts prognosis of patients with locally advanced esophageal squamous cell carcinoma. J Thorac Oncol. 2015;10:1481–9.
Google Scholar
Lin CC, Hsu CH, Cheng JC, Wang HP, Lee JM, Yeh KH, et al. Concurrent chemoradiotherapy with twice weekly paclitaxel and cisplatin followed by esophagectomy for locally advanced esophageal cancer. Ann Oncol. 2007;18:93–8.
Google Scholar
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.
Google Scholar
Huang TC, Liang CW, Li YI, Guo JC, Lin CC, Chen YJ, et al. Prognostic value of PD-L1 expression on immune cells or tumor cells for locally advanced esophageal squamous cell carcinoma in patients treated with neoadjuvant chemoradiotherapy. J Cancer Res Clin Oncol. 2022;148:1803–11.
Google Scholar
Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016;387:1837–46.
Google Scholar
Shah MA, Kojima T, Hochhauser D, Enzinger P, Raimbourg J, Hollebecque A, et al. Efficacy and safety of pembrolizumab for heavily pretreated patients with advanced, metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: the phase 2 KEYNOTE-180 study. JAMA Oncol. 2019;5:546–50.
Google Scholar
Coppola D, Nebozhyn M, Khalil F, Dai H, Yeatman T, Loboda A, et al. Unique ectopic lymph node-like structures present in human primary colorectal carcinoma are identified by immune gene array profiling. Am J Pathol. 2011;179:37–45.
Google Scholar
Messina JL, Fenstermacher DA, Eschrich S, Qu X, Berglund AE, Lloyd MC, et al. 12-Chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy?. Sci Rep. 2012;2:765.
Google Scholar
Feng H, Yang F, Qiao L, Zhou K, Wang J, Zhang J, et al. Prognostic significance of gene signature of tertiary lymphoid structures in patients with lung adenocarcinoma. Front Oncol. 2021;11:693234.
Google Scholar
Prabhakaran S, Rizk VT, Ma Z, Cheng CH, Berglund AE, Coppola D, et al. Evaluation of invasive breast cancer samples using a 12-chemokine gene expression score: correlation with clinical outcomes. Breast Cancer Res. 2017;19:71.
Google Scholar
Sautes-Fridman C, Petitprez F, Calderaro J, Fridman WH. Tertiary lymphoid structures in the era of cancer immunotherapy. Nat Rev Cancer. 2019;19:307–25.
Google Scholar
Li C, Zhao S, Zheng Y, Han Y, Chen X, Cheng Z, et al. Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). Eur J Cancer. 2021;144:232–41.
Google Scholar
Park SY, Hong MH, Kim HR, Lee CG, Cho JH, Cho BC, et al. The feasibility and safety of radical esophagectomy in patients receiving neoadjuvant chemoradiotherapy with pembrolizumab for esophageal squamous cell carcinoma. J Thorac Dis. 2020;12:6426–34.
Google Scholar
He W, Leng X, Mao T, Luo X, Zhou L, Yan J, et al. Toripalimab plus paclitaxel and carboplatin as neoadjuvant therapy in locally advanced resectable esophageal squamous cell carcinoma. Oncologist. 2022;27:e18–e28.
Google Scholar
Yan X, Duan H, Ni Y, Zhou Y, Wang X, Qi H, et al. Tislelizumab combined with chemotherapy as neoadjuvant therapy for surgically resectable esophageal cancer: a prospective, single-arm, phase II study (TD-NICE). Int J Surg. 2022;103:106680.
Google Scholar
Liu J, Yang Y, Liu Z, Fu X, Cai X, Li H, et al. Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma. J Immunother Cancer. 2022;10:e004291.
Liu J, Li J, Lin W, Shao D, Depypere L, Zhang Z, et al. Neoadjuvant camrelizumab plus chemotherapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC-ESCC2019): a multicenter, phase 2 study. Int J Cancer. 2022;151:128–37.
Google Scholar
Qin J, Xue L, Hao A, Guo X, Jiang T, Ni Y, et al. Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: the randomized phase 3 ESCORT-NEO/NCCES01 trial. Nat Med. 2024;30:2549–57.
Google Scholar
Zhang Z, Liu X, Chen D, Yu J. Radiotherapy combined with immunotherapy: the dawn of cancer treatment. Signal Transduct Target Ther. 2022;7:258.
Google Scholar
Saddawi-Konefka R, O’Farrell A, Faraji F, Clubb L, Allevato MM, Jensen SM, et al. Lymphatic-preserving treatment sequencing with immune checkpoint inhibition unleashes cDC1-dependent antitumor immunity in HNSCC. Nat Commun. 2022;13:4298.
Google Scholar
Darragh LB, Gadwa J, Pham TT, Van Court B, Neupert B, Olimpo NA, et al. Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors. Nat Commun. 2022;13:7015.
Google Scholar
Zhao J, Wang K, Li Y, Hu X, Liu H, Zhao J, et al. Impact of radiation dose to immune cells on survival in patients with esophageal cancer receiving neoadjuvant chemoradiotherapy: a retrospective analysis. BMC Cancer. 2025;25:238.
Google Scholar
Tseng I, Chen Y, Ai D, Zhu Z, Zhao W, Fan M, et al. Radiation dose-volume effects on negative tumor-draining lymph nodes impacted T-cell activation and prognosis in esophageal cancer with chemoradiotherapy. Clin Cancer Res. 2025 May 15;31:2024–2033.
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;128:2175–85.
Google Scholar
Fridman WH, Meylan M, Petitprez F, Sun CM, Italiano A, Sautes-Fridman C. B cells and tertiary lymphoid structures as determinants of tumour immune contexture and clinical outcome. Nat Rev Clin Oncol. 2022;19:441–57.
Google Scholar
Schumacher TN, Thommen DS. Tertiary lymphoid structures in cancer. Science. 2022;375:eabf9419.
Google Scholar
Petitprez F, de Reynies A, Keung EZ, Chen TW, Sun CM, Calderaro J, et al. B cells are associated with survival and immunotherapy response in sarcoma. Nature. 2020;577:556–60.
Google Scholar
Vanhersecke L, Brunet M, Guegan JP, Rey C, Bougouin A, Cousin S, et al. Mature tertiary lymphoid structures predict immune checkpoint inhibitor efficacy in solid tumors independently of PD-L1 expression. Nat Cancer. 2021;2:794–802.
Google Scholar
