A high density of tertiary lymphoid structure B cells in lung tumors is associated with increased CD4+T cell receptor repertoire clonality

作者：Wei Zhu, Claire Germain, Zheng Liu, Yinong Sebastian, Priyanka Devi-Marulkar, Samantha Knockaert, Philip Z. Brohawn, Kim Lehmann, Diane Damotte, Pierre Validire, Yihong Yao, Viia Valge-Archer, Scott A. Hammond, Marie‐Caroline Dieu‐Nosjean, Brandon W. Higgs · 发表于：OncoImmunology · 年份：2015 · DOI：10.1080/2162402x.2015.1051922 · 被引用次数：113 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、Immunotherapy and Immune Responses

T and B cell receptor (TCR and BCR, respectively) Vβ or immunoglobulin heavy chain complementarity-determining region 3 sequencing allows monitoring of repertoire changes through recognition, clonal expansion, affinity maturation, and T or B cell activation in response to antigen. TCR and BCR repertoire analysis can advance understanding of antitumor immune responses in the tumor microenvironment. TCR and BCR repertoires of sorted CD4+, CD8+ or CD19+ cells in tumor, non-tumoral distant tissue (NT), and peripheral compartments (blood/draining lymph node [P]) from 47 non-small cell lung cancer (NSCLC) patients (agemedian = 68 y) were sequenced. The clonotype spectra were assessed among different tissues and correlated with clinical and immunological parameters. In all tissues, CD4+ and CD8+ TCR repertoires had greater clonality relative to CD19+ BCR. CD4+ T cells exhibited greater clonality in NT compared to tumor (p = 0.002) and P (p < 0.001), concentrated among older patients (age > 68). Younger patients exhibited greater CD4+ T cell diversity in P compared to older patients (p = 0.05), and greater CD4+ T cell clonality in tumor relative to P (p < 0.001), with fewer shared clonotypes between tumor and P than older patients (p = 0.04). More interestingly, greater CD4+ and CD8+ T cell clonality in tumor and P, respectively (both p = 0.05), correlated with high density of tumor-associated tertiary lymphoid structure (TLS) B cells, a biomarker of higher overall survival in NSCLC....