4.5 Article

CCL19 associates with lymph node metastasis and inferior prognosis in patients with small cell lung cancer

期刊

LUNG CANCER
卷 162, 期 -, 页码 194-202

出版社

ELSEVIER IRELAND LTD
DOI: 10.1016/j.lungcan.2021.11.003

关键词

CCL19; CD8+T cells; Metastasis; Prognosis; Small cell lung cancer

资金

  1. National Natural Science Foundation of China [81772467, 81972167]
  2. Backbone Program of Shanghai Pulmonary Hospital [FKGG1802]
  3. Shanghai Shenkang Hospital Development Center [SHDC12019133]

向作者/读者索取更多资源

The study revealed that CCL19 is associated with lymph node metastasis and poor prognosis in SCLC patients, as its expression promotes tumor progression and metastasis while impairing the function of CD8 + T cells.
Objective: Small cell lung cancer (SCLC) is a systemic disease and most patients have metastases at diagnosis. Better understanding of the underlying mechanisms of SCLC metastasis may provide potential approach to improve clinical outcome. Methods: HTG Edge-seq was used to identify the differential gene expression between primary SCLC lesions and paired metastatic lymph nodes (LN). Overall survival (OS) analysis was performed in patients with different levels of plasma CCL19 concentration. Invasion, migration, proliferation, apoptosis and angiogenesis ability of SCLC cells and function of CD8 + T cells were evaluated in vitro to investigate the mechanism of CCL19 in promoting metastasis. Results: Four chemokines (CCL19, CCL21, CCL8, CCR1) were the most differentially expressed between primary lesions and metastatic LN. CCL19 was further investigated because its mRNA and protein level expression were also validated in four SCLC cell lines (H446, H69, H82, H196). Higher plasma CCL19 was associated with late lymph node (N3) metastasis (training cohort P = 0.044, validation cohort P = 0.020) and shorter OS (training cohort P = 0.040, validation cohort P = 0.047) in SCLC patients. Silencing CCL19 inhibited SCLC cell migration, invasion, proliferation and HUVECs tube formation. Furthermore, we found that CCL19 could decrease percentage of CD8 + Ki67 + and CD8 + GZMB + T cells and increase proportion of CD8 + PD1 + T cells. Conclusion: CCL19 was associated with LN metastasis and poor prognosis in patients with SCLC. Its expression promoted tumor progression and metastasis and impaired the function of CD8 + T cells, suggesting CCL19 might be a potential target for SCLC.

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