Early-stage lung adenocarcinoma with a micropapillary pattern showing a distinct immunogenic tumor microenvironment.

person Yun Han Shengjing Hospital of China Medical University, Shenyang, China info_outline Yun Han, Yue Yu, Chongyuan Xu, Qianru He, Qin Zhang, Qianqian Duan, Dongsheng Chen

Authors person Yun Han Shengjing Hospital of China Medical University, Shenyang, China info_outline Yun Han, Yue Yu, Chongyuan Xu, Qianru He, Qin Zhang, Qianqian Duan, Dongsheng Chen Organizations Shengjing Hospital of China Medical University, Shenyang, China, The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd., the State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, China Abstract Disclosures Research Funding No funding sources reported Background: Lung adenocarcinomas with a micropapillary pattern (MPP) have been suggested to be associated with prognosis. Immune microenvironment plays a critical role in cancer from onset to relapse. However, it is unclear whether MPP can reflect the tumor immune microenvironment (TIME). Methods: A total of 44 stage I lung cancer patients who underwent surgery at Shengjing Hospital of China Medical University were included (with micropapillary pattern, n = 16; without micropapillary pattern, n = 28). Using NanoString nCounter, the gene expression patterns (GEPs) of 289 tumour immune-related genes were examined. Differentially expressed genes(DEGs), estimation of TIME cell infiltration, and TIME signatures between micropapillary and non-micropapillary were assessed. Results: Significant immunological differences were seen between histological subtypes. Differential gene expression analysis showed that KIR2DL3 , MAGEA4 , MELK , CD244 , and 26 other genes were significantly upregulated in the micropapillary group compared with the non-micropapillary group, while PDGFA , RORC , CCL22 , and other seven genes were down-regulated in the micropapillary group. These DEGs were mostly enriched in “leukocyte cell-cell adhesion”, “T cell activation”, “cellular response to chemokine”, and “T cell proliferation” pathways according to GO enrichment analysis. The results of the KEGG analysis revealed that genes were significantly enriched in “Cytokine-cytokine receptor interaction”, “Cell adhesion molecules (CAMs)”, “Chemokine signaling pathway”, and so on. Immune analyses revealed that micropapillary group had a better TIME cell infiltration which are associated with increased CD45, CD8+ T cells, Exhausted CD8, and NK CD56dim cells. Furthermore, the immune signature scores for chemokines, total TILs, and GEP scores were higher in the micropapillary group, indicating increased immune cytotoxic activity. Conclusions: Lung adenocarcinomas with micropapillary pattern were identified as a subtype with enhanced immunogenic tumor microenvironment. According to these results, patients with lung adenocarcinomas that have micropapillary pattern may be a prospective select group who will benefit from adjuvant immunotherapy.