Tumor-draining lymph nodes demonstrate a suppressive immunophenotype in patients with non-small cell lung cancer assessed by endobronchial ultrasound-guided transbronchial needle aspiration: A pilot study

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2019-11, Vol.137, p.94-99
• Main Authors: Murthy, Vivek, Katzman, Daniel P., Tsay, Jun-Chieh J., Bessich, Jamie L., Michaud, Gaetane C., Rafeq, Samaan, Minehart, Janna, Mangalick, Keshav, de Lafaille, M. A. Curotto, Goparaju, Chandra, Pass, Harvey, Sterman, Daniel H.
• Format: Article
• Language: English
• Subjects: Bronchoscopy; EBUS; Endobronchial ultrasound; Interventional pulmonology; Lung cancer; Lymph node; NSCLC; PD-L1
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2019.08.008

•TDLN in patients with NSCLC had a different immunophenotype from paired NDLN.•TDLN had significantly more Tregs and fewer effector CD4 + T cells.•Regional CD4 + T cell depletion was greater when tumor PD-L1 expression was ≥50%.•Immunophenotyping was successfully performed with samples from routine EBUS-TBNA. Tumor draining lymph nodes (TDLN) are key sites of early immunoediting in patients with non-small cell lung cancer (NSCLC) and play an important role in generating anti-tumor immunity. Immune suppression in the tumor microenvironment has prognostic implications and may predict therapeutic response. T cell composition of draining lymph nodes may reflect an immunophenotype with similar prognostic potential which could be measured during standard-of-care bronchoscopic assessment. In this study, we compared the immunophenotype from different sites within individuals to primary tumor characteristics in patients with NSCLC to see whether there were tumor-regional differences in immunophenotype which could be evaluated from transbronchial needle aspirates. Twenty patients were enrolled in this study and had tissue (lymph node aspirates and/or peripheral blood) obtained during standard of care bronchoscopy with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for diagnosis or staging of known or suspected NSCLC. Aspirates and blood underwent flow-assisted cell sorting and a subset of sorted effector T cells underwent RNA quantitation to determine feasibility of this approach. Immunophenotypic patterns from twelve patients with paired data from tumor-draining and non-tumor draining lymph nodes (NDLN) were compared relative to one another and based on PD-L1 immunohistochemistry and primary tumor histology. TDLN had significantly fewer CD4+ T cells (12.68% vs 27%, p = 0.002) and significantly more regulatory T cells (Treg, 12.03% vs 9.52%, p = 0.03) relative to paired NDLN suggesting tumor-regional immunosuppression. There were significantly more Treg in NDLN relative to paired PBMC (9.52% vs 5.6%, p = 0.016). Patients with PD-L1 expression ≥50% had significantly greater tumor-regional CD4+ T cell depletion compared to patients with PD-L1 expression