Abstract 3175: Detection of tumor T-cell clones in mediastinal lymph nodes is associated with lower risk of tumor progression
Authors: Julie A. Rytlewski, Mark P. Rubinstein, Chadrick E. Delinger, Barry Gibney, Erik C. Yusko, Catherine Sanders, John M. Wrangle, Kathryn Lindsey
Journal: Cancer Research (2019)

Abstract Background: The presence of tumor metastases in standard of care lymph node biopsies during surgical resection is used to help determine clinical prognosis. Given the importance of T cells in mediating anti-tumor responses, we sought to assess the clinical significance of T-Cell Receptor (TCR) usage in matched hilar and mediastinal lymph nodes from non-small cell lung cancer (NSCLC) patients. Methods: TCR-Beta chains were quantified by the immunoSEQ® Assay (Adaptive Biotechnologies) in primary early-stage NSCLC tissue, matched hilar lymph nodes (proximal), and matched mediastinal lymph nodes (distal) for 27 patients, who were treated with surgical resection. Patients were selected such that half experienced recurrence and half remained recurrence-free over the 30+ months of patient follow-up. Results: T-cell clonality in resected tumors is significantly correlated (Spearman’s Rho = 0.52, p = 0.0005) but poorly concordant (Pearson’s R2 = 0.14, p = 0.05) with hilar and mediastinal lymph node clonality. The clonality of hilar and mediastinal lymph nodes is both significantly correlated and moderately concordant (Spearman’s Rho = 0.7, p &amp;lt;&amp;lt; 0.01; Pearson’s R2 = 0.44, p = 0.0001). 70-80% of top T-cell clones in tumors were detected in at least one lymph node, and the 100 most abundant tumor clones comprised a median 8.4% and 7.5% of the hilar and mediastinal lymph node repertoires of progression-free subjects, and 7.6% and 6.4% of subjects with tumor progression. Aside from the traditional lymphvascular invasion assessment by histopathology and PET SUVs, the abundance of the top 100 tumor clones and the fraction of top 100 tumor clones detected in the mediastinal lymph node were both independently predictive of early-stage NSCLC progression-free survival (Cox Likelihood p = 0.031 and 0.017, respectively). A 10% increase in the abundance of top 100 tumor clones was associated with a 2.3x increase in risk for progression, suggesting that greater tumor repertoire diversity is favorable in the surgical resection setting. In contrast, for every 10 tumor clones detected in the mediastinal lymph node, the risk of progression decreased by 0.32x, suggesting that increased T-cell trafficking between the tumor and more distant lymph nodes is a favorable prognostic biomarker. Conclusion: The representation of top tumor T-cell clones is fairly similar in hilar and mediastinal lymph nodes. However, the detection of more top tumor clones in the mediastinal lymph nodes is strongly associated with less risk of progression after surgical tumor resection. This biomarker is likely a surrogate for more robust T-cell trafficking between the tumor and lymph circulation and may be a novel hallmark of better patient outcomes. Disclaimers: For Research Use Only. Not for use in diagnostic procedures. Citation Format: Julie A. Rytlewski, Mark P. Rubinstein, Chadrick E. Delinger, Barry Gibney, Erik C. Yusko, Catherine Sanders, John M. Wrangle, Kathryn Lindsey. Detection of tumor T-cell clones in mediastinal lymph nodes is associated with lower risk of tumor progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3175.