High infiltration of mast cells is associated with improved response to adjuvant chemotherapy in gallbladder cancer

• DOI: 10.1111/cas.14302
• Publication Date: 2020-01-11T12:39:15Z
• Authors: Xiaobo Bo; Jie Wang; Changcheng Wang; Lingxi Nan; Zhihui Gao; Yanlei Xin; Min Li; Sheng Shen; Han Liu; Xiaoling Ni; Tao Suo; Dexiang Zhang; Pinxiang Lu; Yueqi Wang; Houbao Liu
• Keywords: Male; Antimetabolites, Antineoplastic; 0303 health sciences; Original Articles; CD8-Positive T-Lymphocytes; Middle Aged; Prognosis; Deoxycytidine; Gemcitabine; 3. Good health; Interferon-gamma; 03 medical and health sciences; Lymphocytes, Tumor-Infiltrating; Chemotherapy, Adjuvant; Humans; Female; Gallbladder Neoplasms; Mast Cells; Signal Transduction

AbstractRecent studies have reported that tumor‐infiltrating mast cells (TIM) play an important role in tumor regression, but the effect of TIM in gallbladder cancer (GBC) remains unclear. The present study aims to investigate the prognostic value of TIM in GBC patients and its responsiveness to gemcitabine‐based adjuvant chemotherapy (ACT). A total of 298 GBC patients from Zhongshan Hospital were recruited for this study. TIM infiltration was measured by immunohistochemical staining. Accumulation of TIM is significantly associated with prolonged overall survival in GBC patients. The benefit from gemcitabine‐based ACT was superior among patients with high infiltration of TIM with GBC. Multivariate analysis identified TIM infiltration as an independent prognostic factor for overall survival. A heatmap showed that TIM‐activated gene signatures were positively correlated with CD8+ T cells' gene signatures. Gene set enrichment analysis (GSEA) suggested that TIM was related to multiple T cell‐related processes and signaling pathways, including the interferon gamma signaling pathway and the leukocyte migration signaling pathway. It was confirmed that CD8+ T cell infiltration was positively correlated with high TIM infiltration in tissue microarray (TMA), suggesting that TIM infiltration was linked to the immune surveillance in GBC. TIM can be used as an independent prognostic factor and a predictor of therapeutic response of gemcitabine‐based ACT in GBC patients, which may mediate immune surveillance by recruiting and activating CD8+ T cells in GBC.