Tumor immune microenvironment and mutational analysis of tracheal adenoid cystic carcinoma

Fei Wang; Xiaohong Xie; Mengmeng Song; Liyan Ji; Ming Liu; Pansong Li; Yanfang Guan; Xinqing Lin; Yinyin Qin; Zhanhong Xie; Jiexia Zhang; Ming Ouyang; Yingying Gu; Haiyi Deng; Xuefeng Xia; Yi Xin; Chengzhi Zhou

doi:10.21037/atm-20-3433

Tumor immune microenvironment and mutational analysis of tracheal adenoid cystic carcinoma

Ann Transl Med. 2020 Jun;8(12):750. doi: 10.21037/atm-20-3433.

Authors

Fei Wang¹, Xiaohong Xie¹, Mengmeng Song², Liyan Ji², Ming Liu¹, Pansong Li², Yanfang Guan², Xinqing Lin¹, Yinyin Qin¹, Zhanhong Xie¹, Jiexia Zhang¹, Ming Ouyang¹, Yingying Gu¹, Haiyi Deng¹, Xuefeng Xia², Yi Xin², Chengzhi Zhou¹

Affiliations

¹ State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, Guangzhou Institute of the Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
² Geneplus-Beijing, Beijing, China.

Abstract

Background: Tracheal adenoid cystic carcinoma (TACC) is the second most common type of cancer in bronchial tumors with poor prognosis. Studies on the genomic profiles and tumor immune microenvironment (TIME) of TACC are still relatively rare.

Methods: Here, we performed whole-exome sequencing (WES), T cell repertoire (TCR) sequencing, and immunohistochemistry (IHC) on the resected tumors and matched peripheral blood leukocytes (PBLs) samples from 25 TACCs collected from April-2010 to Mar-2019.

Results: WES results revealed that LPAR3 and ALPI were recurrently mutated genes, with no classical lung cancer drivers in TACCs (n=8). The median tumor mutation burden (TMB) was 3.67, lower than other solid tumors. Unexpectedly, one patient showed high microsatellite instability (MSI). Recurrent copy number variations (CNVs) affected genes commonly involved in p53, cell cycle, and PI3K-Akt signaling pathways. For TCR estimators of 13 PBLs, the median clonality and Shannon index was 0.15 and 7.02, respectively. Shannon index showed marginally negative association with age (Pearson r =-0.53, P=0.062). Clonotype number and Shannon index of 7 TACC tissues were significantly lower than those of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) (Mann-Whitney test, both P<0.001, both P<0.001). Furthermore, programmed cell death 1 ligand 1 (PD-L1), a vital player in TIME, was negative (tumor proportion score, TPS <1%) in all samples (n=14). Patients with less clonotypes had longer progression-free survival (PFS) than those with more PFS (15.0 vs. 9.5 months, P<0.001, HR 12.5, 95% CI: 0.2-675.7). In particular, the clinical and molecular characteristics of one TACC patient receiving immunotherapy have been explained in detail.

Conclusions: In summary, despite the existence of one patient with MSI-H and chromosome instability, TACC was characterized by a lack of common drivers of lung cancer, negative PD-L1 expression, and low CD3+ and CD8+ T cell infiltration.

Keywords: CD8+ T cell; PD-L1; T cell receptor; Tracheal adenoid cystic carcinoma (TACC); immune checkpoint inhibitors; whole-exome sequencing (WES).