P2.11-05 Peripheral Blood-Based T Cell Receptor Signatures as Potential Biomarkers for Early Diagnosis of Lung Cancer

As more and more solitary pulmonary nodules (SPNs) are detected by low dose CT (LDCT) screening following with high false positive rate, early diagnosis of lung cancer is challenging. Immuno-sequencing provides a feasible strategy for investigate the immune microenvironment of SPNs. However, whether T cell receptor signatures are potential peripheral biomarkers for early diagnosis of lung cancer is unclear. Resected SPNs, which were detected by LDCT screening, and paired peripheral blood from 92 patients were collected, including 27 benign SPNs and 65 lung cancers consisting of 15 LUSC and 50 LUAD. T cell repertoire of tissue and PBMC was evaluated by T cell receptor β genes (TCRβ) sequencing. The GLIPH-based algorithm was referenced to clustered TCR clones according to the motif, and SPN status was predicted by using the clone data from peripheral blood. The Shannon index, indicated diversity in PBMC in malignant patients is lower than that in health cohort (p=8.2e-05). Comparing LUSC and LUAD with Benign patients, lower Shannon index was detected in LUSC patients(p=0.036). With the increase of stage, the Shannon index was gradually decreased(p=0.042). By analysis of the TCR clone similarity of tissues, more similar was found in malignant patients than benign ones (p=2.5e-11), indicating that there are some clones enriched in tumor contributing to the similarity in malignant patients. And then, to get the enriched clones, we built an algorithm which is fishing the clones by enriched motif firstly and by clone incidence secondly. Finally, we got seven enriched clones for number-limited malignant tumors. Seven enriched clones were detected in 34 malignant tissues and 4 benign tissues. Meanwhile, enriched clones also found in PBMC of 25 patients, containing 20 malignant bloods and 5 benign ones, indicating that clones relating to tumor could be a biomarker for peripheral diagnosis for lung cancer. And then we did the validations by independent sets, the sensitivity was 11.9% in 84 lung cancer patients. What’s more, the specificity was 95.8% in 260 healthy cohorts, and 100% in 16 benign nodules. Our preliminary data demonstrate that the distinct immune microenvironment in different SPNs may be associated with particular pathological features. Meanwhile, our approach implied that blood TCR sequencing can provide a high specificity diagnosis of SPNs, accordingly avoiding false positive test and treatment. As the number of patients increases, a more extensive enriched-clone system that covers more population by using our strategy will be constructed.