e18576 Background: Tracheal adenoid cystic carcinoma (TACC) is the second type of cancer in bronchial tumors, has a high rate of postoperative recurrence and poor prognosis for which therapeutic targets are unavailable. Currently, studies were mostly about ACC of salivary gland. Our study is aim to elucidate genomic landscape and predict clinical biomarker of TACC. Methods: We performed whole-exome sequencing (WES), T cell repertoire sequencing (TCR) and immunohistochemistry (IHC) on tumor tissue samples and matched peripheral blood (PB) samples from TACC patients. All patients were followed up for their disease-free survival. Results: 13 cases were enrolled from 2010 to 2019. Median age of 13 TACCs was 35 yrs. 7 patients were female. 12 patients were stage I. In 8 WES samples, TCEB3CL (62%, 5/8), LPAR3 (50%, 4/8), ALPI (38%, 3/8), ARID1A (38%, 3/8) and BCOR (38%, 3/8) mutated most frequently. The median TMB was 3.67 (1.37-6.77) mutations/Mb. 1 patient showed microsatellite instability high (MSI-H). 2 patients with the highest TMB both had POLE mutations. We compared frequency of most mutated genes in our 8 samples with three different ACC types, including 935 ACC of salivary gland cancer, 76 ACC of the lung, and 38 ACC of breast cancer. 7 mutated frequently genes were found both in TACC and other types of ACCs, including ARID1A, BCOR, ARID1B, KMT2C, KMT2D, CREBBP and FAT3. 6 of them were more frequent in TACC. 7 FFPE tumors and 13 PB samples from 13 TACCs were used to investigate immune microenvironment. In 13 PB samples, TCR diversity (shannon index) and clonality was negatively associated with age (Pearson, r = -0.53, p = 0.06; r = 0.53, p = 0.06, respectively). There was no significant association between the other clinical characteristics (gender and smoking history) and any TCR parameter (clonality, clonotype, shannon index). Patients with lower clonotype number had longer DFS than those with higher clonotype number (15.0 vs 9.5 months, p < 0.001, 95% CI, 0.23-675.66, HR, 12.46), while shannon index and clonality was not significantly associated with DFS. Conclusions: The genetic mutations associated with TACC are different from those implicated in non-small cell lung cancer. TCR analysis as a useful of indicator of disease development and prognosis in TACC may be utilized to direct further immunotherapy.