Author:
Yi Bin,Zhao Zhikun,Dong Hui,Yuan Lei,Wu Yingjun,Xu Yun,Jiang Xiaoqing,Sun Chao,Wu Dongfang,Xiao Yajie
Abstract
BackgroundMetastatic 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.Case PresentationWe 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 en bloc 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 (<20%), and negative PD-L1 expression (TC0) were observed in the primary tumor. Likewise, low TMB (5.44 muts/Mb), low MSI (<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+ 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.ConclusionsChemo-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+ T-cells in metastatic node might be indispensable to the durable complete response in this patient.
Subject
Immunology,Immunology and Allergy
Cited by
4 articles.
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