Ibrutinib Does Not Impact CCR7-Mediated Homeostatic Migration in T-Cells from Chronic Lymphocytic Leukemia Patients
Bruton’s tyrosine kinase inhibitor ibrutinib has significantly changed treatment landscape in chronic lymphocytic leukemia (CLL). Growing evidence supports ibrutinib to work beyond the effect on tumor cells by means of, for example, restoring functionality of the T-cell compartment and increasing ci...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/11/2729 |
| _version_ | 1797493917398073344 |
|---|---|
| author | Tamara Mateu-Albero Ana Marcos-Jimenez Stefanie Wissmann Javier Loscertales Fernando Terrón Jens V. Stein Cecilia Muñoz-Calleja Carlos Cuesta-Mateos |
| author_facet | Tamara Mateu-Albero Ana Marcos-Jimenez Stefanie Wissmann Javier Loscertales Fernando Terrón Jens V. Stein Cecilia Muñoz-Calleja Carlos Cuesta-Mateos |
| author_sort | Tamara Mateu-Albero |
| collection | DOAJ |
| description | Bruton’s tyrosine kinase inhibitor ibrutinib has significantly changed treatment landscape in chronic lymphocytic leukemia (CLL). Growing evidence supports ibrutinib to work beyond the effect on tumor cells by means of, for example, restoring functionality of the T-cell compartment and increasing circulating T-cell numbers. Recent evidence suggests T-cell enhanced expansion, rather than increased egress from secondary lymphoid organs (SLO), as a root cause for ibrutinib-induced lymphocytosis. However, whether the latter physiological change is also a consequence of a forced retention in blood remains undisclosed. Since CCR7 is the main chemokine receptor taking over the homing of T-cells from peripheral compartments to lymph nodes and other SLO, we aimed to investigate the impact of ibrutinib on CCR7 functionality in T-cells. To this end, we documented receptor expression in T-cells from a large cohort of ibrutinib-treated CLL patients, and performed different in vivo and in vitro migration models. Overall, our data confirm that CCR7 expression or receptor-mediated migration in CLL T-cells is not affected by ibrutinib. Furthermore, it does not modulate CCR7-driven homing nor nodal interstitial migration. Together, our results support that ibrutinib-induced CLL T-cell accumulation in the blood stream is not derived from an impairment of CCR7-driven recirculation between the SLO and bloodstream, and therefore T-cell expansion is the most plausible cause. |
| first_indexed | 2024-03-10T01:26:52Z |
| format | Article |
| id | doaj.art-7d53c7c70afb482f8fd0abbc0aa2ab5f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T01:26:52Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-7d53c7c70afb482f8fd0abbc0aa2ab5f2023-11-23T13:50:07ZengMDPI AGCancers2072-66942022-05-011411272910.3390/cancers14112729Ibrutinib Does Not Impact CCR7-Mediated Homeostatic Migration in T-Cells from Chronic Lymphocytic Leukemia PatientsTamara Mateu-Albero0Ana Marcos-Jimenez1Stefanie Wissmann2Javier Loscertales3Fernando Terrón4Jens V. Stein5Cecilia Muñoz-Calleja6Carlos Cuesta-Mateos7Immunology Department, Hospital Universitario de La Princesa, IIS-IP, 28006 Madrid, SpainImmunology Department, Hospital Universitario de La Princesa, IIS-IP, 28006 Madrid, SpainDepartment of Oncology, Microbiology and Immunology, University of Fribourg, CH-1700 Freiburg, SwitzerlandHematology Department, Hospital Universitario de La Princesa, IIS-IP, 28006 Madrid, SpainIMMED S.L., Immunological and Medicinal Products, C/Velázquez 57, 6º derecha, 28001 Madrid, SpainDepartment of Oncology, Microbiology and Immunology, University of Fribourg, CH-1700 Freiburg, SwitzerlandImmunology Department, Hospital Universitario de La Princesa, IIS-IP, 28006 Madrid, SpainImmunology Department, Hospital Universitario de La Princesa, IIS-IP, 28006 Madrid, SpainBruton’s tyrosine kinase inhibitor ibrutinib has significantly changed treatment landscape in chronic lymphocytic leukemia (CLL). Growing evidence supports ibrutinib to work beyond the effect on tumor cells by means of, for example, restoring functionality of the T-cell compartment and increasing circulating T-cell numbers. Recent evidence suggests T-cell enhanced expansion, rather than increased egress from secondary lymphoid organs (SLO), as a root cause for ibrutinib-induced lymphocytosis. However, whether the latter physiological change is also a consequence of a forced retention in blood remains undisclosed. Since CCR7 is the main chemokine receptor taking over the homing of T-cells from peripheral compartments to lymph nodes and other SLO, we aimed to investigate the impact of ibrutinib on CCR7 functionality in T-cells. To this end, we documented receptor expression in T-cells from a large cohort of ibrutinib-treated CLL patients, and performed different in vivo and in vitro migration models. Overall, our data confirm that CCR7 expression or receptor-mediated migration in CLL T-cells is not affected by ibrutinib. Furthermore, it does not modulate CCR7-driven homing nor nodal interstitial migration. Together, our results support that ibrutinib-induced CLL T-cell accumulation in the blood stream is not derived from an impairment of CCR7-driven recirculation between the SLO and bloodstream, and therefore T-cell expansion is the most plausible cause.https://www.mdpi.com/2072-6694/14/11/2729T-cellCCR7CLLibrutiniblymph nodemigration |
| spellingShingle | Tamara Mateu-Albero Ana Marcos-Jimenez Stefanie Wissmann Javier Loscertales Fernando Terrón Jens V. Stein Cecilia Muñoz-Calleja Carlos Cuesta-Mateos Ibrutinib Does Not Impact CCR7-Mediated Homeostatic Migration in T-Cells from Chronic Lymphocytic Leukemia Patients Cancers T-cell CCR7 CLL ibrutinib lymph node migration |
| title | Ibrutinib Does Not Impact CCR7-Mediated Homeostatic Migration in T-Cells from Chronic Lymphocytic Leukemia Patients |
| title_full | Ibrutinib Does Not Impact CCR7-Mediated Homeostatic Migration in T-Cells from Chronic Lymphocytic Leukemia Patients |
| title_fullStr | Ibrutinib Does Not Impact CCR7-Mediated Homeostatic Migration in T-Cells from Chronic Lymphocytic Leukemia Patients |
| title_full_unstemmed | Ibrutinib Does Not Impact CCR7-Mediated Homeostatic Migration in T-Cells from Chronic Lymphocytic Leukemia Patients |
| title_short | Ibrutinib Does Not Impact CCR7-Mediated Homeostatic Migration in T-Cells from Chronic Lymphocytic Leukemia Patients |
| title_sort | ibrutinib does not impact ccr7 mediated homeostatic migration in t cells from chronic lymphocytic leukemia patients |
| topic | T-cell CCR7 CLL ibrutinib lymph node migration |
| url | https://www.mdpi.com/2072-6694/14/11/2729 |
| work_keys_str_mv | AT tamaramateualbero ibrutinibdoesnotimpactccr7mediatedhomeostaticmigrationintcellsfromchroniclymphocyticleukemiapatients AT anamarcosjimenez ibrutinibdoesnotimpactccr7mediatedhomeostaticmigrationintcellsfromchroniclymphocyticleukemiapatients AT stefaniewissmann ibrutinibdoesnotimpactccr7mediatedhomeostaticmigrationintcellsfromchroniclymphocyticleukemiapatients AT javierloscertales ibrutinibdoesnotimpactccr7mediatedhomeostaticmigrationintcellsfromchroniclymphocyticleukemiapatients AT fernandoterron ibrutinibdoesnotimpactccr7mediatedhomeostaticmigrationintcellsfromchroniclymphocyticleukemiapatients AT jensvstein ibrutinibdoesnotimpactccr7mediatedhomeostaticmigrationintcellsfromchroniclymphocyticleukemiapatients AT ceciliamunozcalleja ibrutinibdoesnotimpactccr7mediatedhomeostaticmigrationintcellsfromchroniclymphocyticleukemiapatients AT carloscuestamateos ibrutinibdoesnotimpactccr7mediatedhomeostaticmigrationintcellsfromchroniclymphocyticleukemiapatients |