{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T22:30:56Z","timestamp":1770330656834,"version":"3.49.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T00:00:00Z","timestamp":1644883200000},"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><jats:title>Background<\/jats:title><jats:p>Metastatic gallbladder carcinoma (GBC) is one of the most aggressive malignancies. As GBC is usually diagnosed with distant metastases, only a few patients can receive R0 resection and the relapse rate remains high. Programmed cell death protein 1 (PD-1) blockade therapy has provided encouraging long-term outcomes in a subset of patients in many cancers. However, the data on efficacy of PD-1 blockade in GBC are very limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case Presentation<\/jats:title><jats:p>We herein reported a stage IVB GBC patient with localized primary tumor and distant lymph node metastasis. Except for the unresectable multiple metastatic nodes including distant nodes, a complete resection of primary tumor <jats:italic>en bloc<\/jats:italic> with partial segment 4B+5 was performed. Tumor tissues of primary tumor and one metastatic lymph node were collected to perform whole-exome sequencing, RNA-seq, and immunohistochemistry. Low TMB (5.38 muts\/Mb), low MSI (&amp;lt;20%), and negative PD-L1 expression (TC0) were observed in the primary tumor. Likewise, low TMB (5.44 muts\/Mb), low MSI (&amp;lt;20%), and low PD-L1 expression (TC2) presented in the metastatic lymph node. Besides, low genetic intratumor heterogeneity exhibited between the primary and metastatic tumors in this patient. In contrast to the primary tumor, higher-level CD8<jats:sup>+<\/jats:sup> T cell infiltration was revealed in the tumor microenvironment of the metastatic lymph node. Then, chemo-immunotherapy using S1 and anti-PD-1 antibody pembrolizumab was administrated as the first-line treatment for the residual metastatic nodes. Complete response was achieved after 7 courses and has lasted for 32 months up to present. Additionally, blood samples during treatment were further analyzed for immune repertoire sequencing, showing that several T cell receptor clones in metastatic lymph node were predominant in blood during the combined anti-PD-1 treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Chemo-immunotherapy may provide a potential curative option for the lymph node metastases of gallbladder cancer. The low intratumor heterogeneity and high level of infiltrating CD8<jats:sup>+<\/jats:sup> T-cells in metastatic node might be indispensable to the durable complete response in this patient.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.820566","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T05:44:18Z","timestamp":1644903858000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Case Report: Durable Complete Response After Combined Immunotherapy Following Resection of Primary Tumor in a Gallbladder Cancer Patient With Distant Metastatic Lymph Nodes of Favorable Immune-Microenvironment"],"prefix":"10.3389","volume":"13","author":[{"given":"Bin","family":"Yi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhikun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingjun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqing","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongfang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yajie","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.51.6.349","article-title":"Epidemiology 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