title: Characterization of chemokines and adhesion molecules associated with T cell presence in tertiary lymphoid structures in human lung cancer.
abstract: De novo formation of tertiary lymphoid structures (TLS) has been described in lung cancers. Intratumoral TLS seem to be functional and are associated with a long-term survival for lung cancer patients, suggesting that they represent an activation site for tumor-specific T cells. Here, we characterized T-cell recruitment to TLS in human lung cancer to identify the adhesion molecules and chemoattractants orchestrating this migration. We found that most TLS T cells were CD62L+ and mainly of CD4+ memory phenotype, but naive T cells were highly enriched in these structures as compared with the rest of the tumor. A specific gene expression signature associated with T cell presence was identified in TLS, which included chemokines (CCL19, CCL21, CXCL13, CCL17, CCL22, and IL16), adhesion molecules (ICAM-2, ICAM-3, VCAM-1, and MAdCAM-1) and integrins (alphaL, alpha4, and alphaD). The presence of the corresponding receptors on TLS T cells was confirmed. Intratumoral PNAd+ high endothelial venules also were exclusively associated with TLS and colocalized with CD62L+ lymphocytes. Together, these data bring new insights into the T-cell recruitment to intratumoral TLS and suggest that blood T cell enter into TLS via high endothelial venules, which represent a new gateway for T cells to the tumor. Findings identify the molecules that mediate migration of tumor-specific T cells into TLS where T cell priming occurs, suggesting new strategies to enhance the efficacy of cancer immunotherapies.
authors: Laboratory Immunological Microenvironment and Tumors, INSERM U872, Cordeliers Research Centre, Paris, France.
authors: Luc
authors: L
authors: de Chaisemartin
authors: Jérémy
authors: J
authors: Goc
authors: Diane
authors: D
authors: Damotte
authors: Pierre
authors: P
authors: Validire
authors: Pierre
authors: P
authors: Magdeleinat
authors: Marco
authors: M
authors: Alifano
authors: Isabelle
authors: I
authors: Cremer
authors: Wolf-Herman
authors: WH
authors: Fridman
authors: Catherine
authors: C
authors: Sautès-Fridman
authors: Marie-Caroline
authors: MC
authors: Dieu-Nosjean
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology / Q000502:physiology; D018925:Chemokines / Q000276:immunology / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D018925:Chemokines; D016023:Integrins