Tertiary Lymphoid Structure-B Cells Narrow Regulatory T Cells Impact in Lung Cancer Patients
| Autor: | Claire, Germain, Priyanka, Devi-Marulkar, Samantha, Knockaert, Jérôme, Biton, Hélène, Kaplon, Laïla, Letaïef, Jérémy, Goc, Agathe, Seguin-Givelet, Dominique, Gossot, Nicolas, Girard, Pierre, Validire, Marine, Lefèvre, Diane, Damotte, Marco, Alifano, François M, Lemoine, Keith E, Steele, Jean-Luc, Teillaud, Scott A, Hammond, Marie-Caroline, Dieu-Nosjean |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male B-Lymphocytes B cell regulatory T cell Lung Neoplasms Immunology immune microenvironment Middle Aged Lymphocyte Activation T-Lymphocytes Regulatory lung cancer Lymphocytes Tumor-Infiltrating Carcinoma Non-Small-Cell Lung Tumor Microenvironment Humans tertiary lymphoid structure Transcriptome immune checkpoint Aged Retrospective Studies Original Research |
| Zdroj: | Frontiers in Immunology |
| ISSN: | 1664-3224 |
| Popis: | The presence of tertiary lymphoid structures (TLS) in the tumor microenvironment is associated with better clinical outcome in many cancers. In non-small cell lung cancer (NSCLC), we have previously showed that a high density of B cells within TLS (TLS-B cells) is positively correlated with tumor antigen-specific antibody responses and increased intratumor CD4+ T cell clonality. Here, we investigated the relationship between the presence of TLS-B cells and CD4+ T cell profile in NSCLC patients. The expression of immune-related genes and proteins on B cells and CD4+ T cells was analyzed according to their relationship to TLS-B density in a prospective cohort of 56 NSCLC patients. We observed that tumor-infiltrating T cells showed marked differences according to TLS-B cell presence, with higher percentages of naïve, central-memory, and activated CD4+ T cells and lower percentages of both immune checkpoint (ICP)-expressing CD4+ T cells and regulatory T cells (Tregs) in the TLS-Bhigh tumors. A retrospective study of 538 untreated NSCLC patients showed that high TLS-B cell density was even able to counterbalance the deleterious impact of high Treg density on patient survival, and that TLS-Bhigh Treglow patients had the best clinical outcomes. Overall, the correlation between the density of TLS-Bhigh tumors with early differentiated, activated and non-regulatory CD4+ T cell cells suggest that B cells may play a central role in determining protective T cell responses in NSCLC patients. |
| Databáze: | OpenAIRE |
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