Frontiers in Immunology (Mar 2021)
Tertiary Lymphoid Structure-B Cells Narrow Regulatory T Cells Impact in Lung Cancer Patients
- Claire Germain,
- Claire Germain,
- Claire Germain,
- Claire Germain,
- Claire Germain,
- Priyanka Devi-Marulkar,
- Priyanka Devi-Marulkar,
- Priyanka Devi-Marulkar,
- Samantha Knockaert,
- Samantha Knockaert,
- Samantha Knockaert,
- Jérôme Biton,
- Jérôme Biton,
- Jérôme Biton,
- Hélène Kaplon,
- Hélène Kaplon,
- Hélène Kaplon,
- Laïla Letaïef,
- Laïla Letaïef,
- Laïla Letaïef,
- Laïla Letaïef,
- Laïla Letaïef,
- Jérémy Goc,
- Jérémy Goc,
- Jérémy Goc,
- Agathe Seguin-Givelet,
- Agathe Seguin-Givelet,
- Agathe Seguin-Givelet,
- Dominique Gossot,
- Dominique Gossot,
- Nicolas Girard,
- Pierre Validire,
- Pierre Validire,
- Marine Lefèvre,
- Marine Lefèvre,
- Marine Lefèvre,
- Diane Damotte,
- Diane Damotte,
- Diane Damotte,
- Diane Damotte,
- Marco Alifano,
- Marco Alifano,
- Marco Alifano,
- Marco Alifano,
- François M. Lemoine,
- François M. Lemoine,
- Keith E. Steele,
- Jean-Luc Teillaud,
- Jean-Luc Teillaud,
- Jean-Luc Teillaud,
- Jean-Luc Teillaud,
- Jean-Luc Teillaud,
- Scott A. Hammond,
- Marie-Caroline Dieu-Nosjean,
- Marie-Caroline Dieu-Nosjean,
- Marie-Caroline Dieu-Nosjean,
- Marie-Caroline Dieu-Nosjean,
- Marie-Caroline Dieu-Nosjean
Affiliations
- Claire Germain
- Sorbonne Université, UMRS 1135, Faculté de Médecine Sorbonne Université, Paris, France
- Claire Germain
- Laboratory “Immune Microenvironment and Immunotherapy”, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses Paris (CIMI-Paris), Paris, France
- Claire Germain
- Sorbonne Université, UMRS 1138, Paris, France
- Claire Germain
- Laboratory “Cancer, Immune Control, and Escape”, INSERM U1138, Cordeliers Research Center, Paris, France
- Claire Germain
- Université de Paris, UMRS 1138, Paris, France
- Priyanka Devi-Marulkar
- Sorbonne Université, UMRS 1138, Paris, France
- Priyanka Devi-Marulkar
- Laboratory “Cancer, Immune Control, and Escape”, INSERM U1138, Cordeliers Research Center, Paris, France
- Priyanka Devi-Marulkar
- Université de Paris, UMRS 1138, Paris, France
- Samantha Knockaert
- Sorbonne Université, UMRS 1138, Paris, France
- Samantha Knockaert
- Laboratory “Cancer, Immune Control, and Escape”, INSERM U1138, Cordeliers Research Center, Paris, France
- Samantha Knockaert
- Université de Paris, UMRS 1138, Paris, France
- Jérôme Biton
- Sorbonne Université, UMRS 1138, Paris, France
- Jérôme Biton
- Laboratory “Cancer, Immune Control, and Escape”, INSERM U1138, Cordeliers Research Center, Paris, France
- Jérôme Biton
- Université de Paris, UMRS 1138, Paris, France
- Hélène Kaplon
- Sorbonne Université, UMRS 1138, Paris, France
- Hélène Kaplon
- Laboratory “Cancer, Immune Control, and Escape”, INSERM U1138, Cordeliers Research Center, Paris, France
- Hélène Kaplon
- Université de Paris, UMRS 1138, Paris, France
- Laïla Letaïef
- Sorbonne Université, UMRS 1135, Faculté de Médecine Sorbonne Université, Paris, France
- Laïla Letaïef
- Laboratory “Immune Microenvironment and Immunotherapy”, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses Paris (CIMI-Paris), Paris, France
- Laïla Letaïef
- Sorbonne Université, UMRS 1138, Paris, France
- Laïla Letaïef
- Laboratory “Cancer, Immune Control, and Escape”, INSERM U1138, Cordeliers Research Center, Paris, France
- Laïla Letaïef
- Université de Paris, UMRS 1138, Paris, France
- Jérémy Goc
- Sorbonne Université, UMRS 1138, Paris, France
- Jérémy Goc
- Laboratory “Cancer, Immune Control, and Escape”, INSERM U1138, Cordeliers Research Center, Paris, France
- Jérémy Goc
- Université de Paris, UMRS 1138, Paris, France
- Agathe Seguin-Givelet
- Laboratory “Immune Microenvironment and Immunotherapy”, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses Paris (CIMI-Paris), Paris, France
- Agathe Seguin-Givelet
- Thoracic Department, Curie-Montsouris Thorax Institute, Institut Mutualiste Montsouris, Paris, France
- Agathe Seguin-Givelet
- Université Sorbonne Paris Nord, Sorbonne Paris Cité, Faculté de Médecine SMBH, Bobigny, France
- Dominique Gossot
- Laboratory “Immune Microenvironment and Immunotherapy”, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses Paris (CIMI-Paris), Paris, France
- Dominique Gossot
- Thoracic Department, Curie-Montsouris Thorax Institute, Institut Mutualiste Montsouris, Paris, France
- Nicolas Girard
- Oncology Department, Curie-Montsouris Thorax Institute, Institut Curie, Paris, France
- Pierre Validire
- Laboratory “Cancer, Immune Control, and Escape”, INSERM U1138, Cordeliers Research Center, Paris, France
- Pierre Validire
- Department of Pathology, Institut Mutualiste Montsouris, Paris, France
- Marine Lefèvre
- Laboratory “Immune Microenvironment and Immunotherapy”, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses Paris (CIMI-Paris), Paris, France
- Marine Lefèvre
- Thoracic Department, Curie-Montsouris Thorax Institute, Institut Mutualiste Montsouris, Paris, France
- Marine Lefèvre
- Department of Pathology, Institut Mutualiste Montsouris, Paris, France
- Diane Damotte
- Sorbonne Université, UMRS 1138, Paris, France
- Diane Damotte
- Laboratory “Cancer, Immune Control, and Escape”, INSERM U1138, Cordeliers Research Center, Paris, France
- Diane Damotte
- Université de Paris, UMRS 1138, Paris, France
- Diane Damotte
- 0Department of Pathology, Assistance Publique-Hopitaux de Paris (AP-HP), Cochin Hospital, Paris, France
- Marco Alifano
- Sorbonne Université, UMRS 1138, Paris, France
- Marco Alifano
- Laboratory “Cancer, Immune Control, and Escape”, INSERM U1138, Cordeliers Research Center, Paris, France
- Marco Alifano
- Université de Paris, UMRS 1138, Paris, France
- Marco Alifano
- 1Department of Thoracic Surgery, Assistance Publique-Hopitaux de Paris (AP-HP), Cochin Hospital, Paris, France
- François M. Lemoine
- Sorbonne Université, UMRS 1135, Faculté de Médecine Sorbonne Université, Paris, France
- François M. Lemoine
- Laboratory “Immune Microenvironment and Immunotherapy”, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses Paris (CIMI-Paris), Paris, France
- Keith E. Steele
- 2Oncology Translational Sciences, AstraZeneca, Gaithersburg, MD, United States
- Jean-Luc Teillaud
- Sorbonne Université, UMRS 1135, Faculté de Médecine Sorbonne Université, Paris, France
- Jean-Luc Teillaud
- Laboratory “Immune Microenvironment and Immunotherapy”, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses Paris (CIMI-Paris), Paris, France
- Jean-Luc Teillaud
- Sorbonne Université, UMRS 1138, Paris, France
- Jean-Luc Teillaud
- Laboratory “Cancer, Immune Control, and Escape”, INSERM U1138, Cordeliers Research Center, Paris, France
- Jean-Luc Teillaud
- Université de Paris, UMRS 1138, Paris, France
- Scott A. Hammond
- 3Oncology Research, AstraZeneca, Gaithersburg, MD, United States
- Marie-Caroline Dieu-Nosjean
- Sorbonne Université, UMRS 1135, Faculté de Médecine Sorbonne Université, Paris, France
- Marie-Caroline Dieu-Nosjean
- Laboratory “Immune Microenvironment and Immunotherapy”, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses Paris (CIMI-Paris), Paris, France
- Marie-Caroline Dieu-Nosjean
- Sorbonne Université, UMRS 1138, Paris, France
- Marie-Caroline Dieu-Nosjean
- Laboratory “Cancer, Immune Control, and Escape”, INSERM U1138, Cordeliers Research Center, Paris, France
- Marie-Caroline Dieu-Nosjean
- Université de Paris, UMRS 1138, Paris, France
- DOI
- https://doi.org/10.3389/fimmu.2021.626776
- Journal volume & issue
-
Vol. 12
Abstract
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.
Keywords
- B cell
- immune checkpoint
- immune microenvironment
- lung cancer
- regulatory T cell
- tertiary lymphoid structure