Lung cancer-associated T cell repertoire as potential biomarker for early detection of stage I lung cancer

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 162; pp. 16 - 22
• Main Authors: Li, Min, Zhang, Chunliu, Deng, Shichao, Li, Li, Liu, Shiqing, Bai, Jing, Xu, Yaping, Guan, Yanfang, Xia, Xuefeng, Sun, Lunquan, Carbone, David P., Hu, Chengping
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.12.2021
• Subjects: Biomarker; Biomarkers; Early detection; Early Detection of Cancer; Humans; Lung cancer; Lung cancer-associated TCRs; Lung Neoplasms - diagnosis; Stage I; T-Lymphocytes; Tomography, X-Ray Computed; BPN; TCR; Biomarker; NSCLC; TRB; MOI; Lung cancer; Lung cancer-associated TCRs; TCRβ; LDCT; LC-aMotif; PBMC; LC-aTCR; ctDNA; Early detection; LUAD; CT; Stage I; LUSC; NLST; CTCs
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2021.09.017

•Immune microenvironment changes can occur at very low tumor burden, even in stage I lung cancer.•Lung cancer-associated TCR (LC-aTCR) is a candidate biomarker for early detection of stage I lung cancer with high sensitivity and specificity. Early detection of lung cancer in asymptomatic patients remains challenging, especially for stage I. Considering the substantial interaction with tumor immunogenicity, we hypothesized that lung cancer-associated TCR (LC-aTCR) may serve as potential biomarker in early detection of stage I lung cancer. Individuals who received low-dose computed tomography (LDCT) screening were enrolled in the study. Surgical tissues and peripheral blood specimens were collected and performed with DNA-based T cell repertoire (TCR) sequencing. The motif-based algorithm was used to deconstruct specific lung cancer-associated TCRs (LC-aTCRs). A total of 146 individuals participating in the real-world LDCT screening project were enrolled in this study, including 52 patients with pathologically-confirmed stage I lung cancer and 94 non-cancer controls. We developed a motif-based algorithm to define 80 LC-aTCRs in the training cohort. Moreover, in the validation cohort, high sensitivity and specificity was showed in stage I lung cancer with 72% and 91% respectively, and the AUC of the ROC curve was 0.91 (95% CI: 0.85 ∼ 0.96). This work provides inspiration for stage I lung cancer detection by using blood TCR profiling data. The combination of TCR-based assay and routine screening deserves further testing in larger cohorts.