A prospective, observational study investigating the peripheral TCR repertoire as a predictive biomarker in SCLC via collection of samples pre- and post-ICI administration in first-line extensive disease is warranted.Īlthough immune checkpoint inhibitors (ICIs) represent an opportunity to harness the immune system to target cancer cells in a variety of disease settings, only a subset of patients with small cell lung cancer (SCLC) achieve clinical benefit from ICIs ( 1).What is the implication, and what should change now? We report the second study in SCLC characterizing peripheral TCR repertoires and investigating associations between TCR diversity and clinical outcomes.Limited data in SCLC demonstrates a cold and heterogeneous intratumoral TCR repertoire. Characteristics of intratumoral and circulating TCR repertoires predict clinical outcomes in non-small cell lung cancer patients treated with immune checkpoint inhibitors (ICIs).Concordant with one previous report, we observed an exceptional responder with high TCR diversity.No statistically significant association was observed between peripheral T-cell receptor (TCR) diversity and clinical outcomes in this limited cohort of 14 patients with small cell lung cancer (SCLC).With a limited sample size, no statistically significant associations between peripheral TCR diversity and clinical outcomes were observed, though further study is warranted. Kaplan-Meier curve and log-rank analysis did not identify a statistical difference in progression-free survival (PFS) (P=0.900) or overall survival (OS) (P=0.200) between high and low on-treatment TCR diversity groups, although the high diversity group exhibited a trend toward increased OS.Ĭonclusions: We report the second study investigating peripheral TCR repertoire diversity in SCLC. Results: Patients with stable versus progressive and limited versus extensive stage disease did not demonstrate significant differences in V gene usage. Unique TCR clonotypes were defined by identical CDR3, V gene, and J gene nucleotide sequences of the beta chain and subsequently used to calculate TCR diversity indices. Targeted next-generation sequencing of TCR beta and alpha chains of peripheral blood samples was performed. Methods: SCLC patients with limited (n=4) and extensive (n=10) stage disease were prospectively enrolled for blood collection and chart review. Recognizing a knowledge gap, we sought to characterize circulating TCR repertoires and their relationship with clinical outcomes in SCLC. Characteristics of peripheral and intratumoral T-cell receptor (TCR) repertoires have been shown to predict clinical outcomes in non-small cell lung cancer (NSCLC). Iams, 0000-0003-2109-298X.īackground: Identifying a circulating biomarker predictive of immune checkpoint inhibitor (ICI) benefit in patients with small cell lung cancer (SCLC) remains an unmet need. Iams 2,3^ġ Vanderbilt University School of Medicine, Nashville, TN, USA Ģ Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA ģ Vanderbilt-Ingram Cancer Center, Nashville, TN, USA Ĥ Resolution Bioscience, Kirkland, WA, USAĬontributions: (I) Conception and design: ML Balbach, WT Iams, ML Axelrod (II) Administrative support: ML Balbach, WT Iams (III) Provision of study materials or patients: WT Iams, JM Balko, M Li (IV) Collection and assembly of data: ML Axelrod, A Bankhead, T Shaffer, L Lim, J Guo, M Li (V) Data analysis and interpretation: ML Balbach, ML Axelrod, WT Iams (VI) Manuscript writing: All authors (VII) Final approval of manuscript: All authors. Balko 2,3^, Armand Bankhead 4, Tristan Shaffer 4, Lee Lim 4, Jiannan Guo 4, Jennifer Hernandez 4, Mark Li 4, Wade T.

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Immune repertoire and disease