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. (November 2019)

• Record Type: Journal Article
• 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.
• Is Part Of: Lung cancer. Volume 137(2019)
• Page Start: 94
• Page End: 99
• Publication Date: 2019-11
• Subjects: Lung cancer -- Lymph node -- Bronchoscopy -- Endobronchial ultrasound -- NSCLC -- EBUS -- Interventional pulmonology -- PD-L1; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2019.08.008
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: 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. Abstract: Objectives: 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. Materials and Methods: 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. Results: 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 <50% (−35.98% vs −1.89%, p = 0.0357; negative values represent absolute difference between paired TDLN and NDLN). Conclusions: In patients with NSCLC, TDLN have a suppressive immunophenotype correlating with tumor PD-L1 status and can be assessed during routine EBUS-TBNA.