Characterization of chemokines and adhesion molecules associated with T cell presence in tertiary lymphoid structures in human lung cancer

L de Chaisemartin, J Goc, D Damotte, P Validire… - Cancer research, 2011 - AACR
L de Chaisemartin, J Goc, D Damotte, P Validire, P Magdeleinat, M Alifano, I Cremer
Cancer research, 2011AACR
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 …
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. Cancer Res; 71(20); 6391–9. ©2011 AACR.
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