Long-Term Host Immune Modulation Following Tisagenlecleucel Administration in Patients with Diffuse Large B-Cell Lymphoma and B-Lineage Acute Lymphoblastic Leukemia
<b>Background:</b> Chimeric antigen receptor (CAR)-T cells represent a potentially curative strategy for patients with relapsed or refractory (R/R) B-cell malignancies. To elucidate a possible host immune activation following CAR-T-cell infusion, we investigated the effects of tisagenlec...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/9/2411 |
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| author | Anna Guarini Giulia Radice Nadia Peragine Chiara Buracchi Maria Stefania De Propris Alice Di Rocco Arianna Di Rocco Sabina Chiaretti Alex Moretti Sara Napolitano Maurizio Martelli Adriana Balduzzi Giuseppe Gaipa Andrea Biondi Robin Foà |
| author_facet | Anna Guarini Giulia Radice Nadia Peragine Chiara Buracchi Maria Stefania De Propris Alice Di Rocco Arianna Di Rocco Sabina Chiaretti Alex Moretti Sara Napolitano Maurizio Martelli Adriana Balduzzi Giuseppe Gaipa Andrea Biondi Robin Foà |
| author_sort | Anna Guarini |
| collection | DOAJ |
| description | <b>Background:</b> Chimeric antigen receptor (CAR)-T cells represent a potentially curative strategy for patients with relapsed or refractory (R/R) B-cell malignancies. To elucidate a possible host immune activation following CAR-T-cell infusion, we investigated the effects of tisagenlecleucel administration on the patients’ immune populations in 25 patients with R/R diffuse large B-cell lymphoma (DLBCL) and B-lineage acute lymphoblastic leukemia (B-ALL). <b>Methods:</b> The modulation of CAR-T cells over time, the numeric changes, as well as the cytokine production capability of different lymphocyte populations and circulating cytokine levels, were analyzed. <b>Results:</b> Our results confirmed the ability of tisagenlecleucel to control the disease, with an overall response observed in 84.6% of DLBCL and in 91.7% of B-ALL patients at 1-month post-infusion, and showed that most patients who subsequently relapsed could undergo further treatment. Interestingly, we could document a significant increase in CD3<sup>+</sup>, CD4<sup>+</sup>, CD8<sup>+</sup>, and NK cells over time, as well as a decrease in Treg cells, and an increased IFNγ and TNFα production by T lymphocytes. <b>Conclusions:</b> Taken together, our results indicate that in patients with DLBCL and B-ALL, the administration of tisagenlecleucel is capable of inducing a marked and prolonged in vivo modulation/reshaping of the host immune system, both in children and adults. |
| first_indexed | 2024-03-11T04:22:50Z |
| format | Article |
| id | doaj.art-04f049bdefc54398b6baebf7bf965367 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T04:22:50Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-04f049bdefc54398b6baebf7bf9653672023-11-17T22:39:22ZengMDPI AGCancers2072-66942023-04-01159241110.3390/cancers15092411Long-Term Host Immune Modulation Following Tisagenlecleucel Administration in Patients with Diffuse Large B-Cell Lymphoma and B-Lineage Acute Lymphoblastic LeukemiaAnna Guarini0Giulia Radice1Nadia Peragine2Chiara Buracchi3Maria Stefania De Propris4Alice Di Rocco5Arianna Di Rocco6Sabina Chiaretti7Alex Moretti8Sara Napolitano9Maurizio Martelli10Adriana Balduzzi11Giuseppe Gaipa12Andrea Biondi13Robin Foà14Hematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, ItalyHematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, ItalyHematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, ItalyTettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, ItalyHematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, ItalyHematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, ItalyDepartment of Public Health and Infectious Diseases, Sapienza University, 00185 Rome, ItalyHematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, ItalyTettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, ItalyPediatrics, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, ItalyHematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, ItalyPediatrics, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, ItalyTettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, ItalyPediatrics, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, ItalyHematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, Italy<b>Background:</b> Chimeric antigen receptor (CAR)-T cells represent a potentially curative strategy for patients with relapsed or refractory (R/R) B-cell malignancies. To elucidate a possible host immune activation following CAR-T-cell infusion, we investigated the effects of tisagenlecleucel administration on the patients’ immune populations in 25 patients with R/R diffuse large B-cell lymphoma (DLBCL) and B-lineage acute lymphoblastic leukemia (B-ALL). <b>Methods:</b> The modulation of CAR-T cells over time, the numeric changes, as well as the cytokine production capability of different lymphocyte populations and circulating cytokine levels, were analyzed. <b>Results:</b> Our results confirmed the ability of tisagenlecleucel to control the disease, with an overall response observed in 84.6% of DLBCL and in 91.7% of B-ALL patients at 1-month post-infusion, and showed that most patients who subsequently relapsed could undergo further treatment. Interestingly, we could document a significant increase in CD3<sup>+</sup>, CD4<sup>+</sup>, CD8<sup>+</sup>, and NK cells over time, as well as a decrease in Treg cells, and an increased IFNγ and TNFα production by T lymphocytes. <b>Conclusions:</b> Taken together, our results indicate that in patients with DLBCL and B-ALL, the administration of tisagenlecleucel is capable of inducing a marked and prolonged in vivo modulation/reshaping of the host immune system, both in children and adults.https://www.mdpi.com/2072-6694/15/9/2411CAR-T cellsDLBCLB-ALLimmune modulation |
| spellingShingle | Anna Guarini Giulia Radice Nadia Peragine Chiara Buracchi Maria Stefania De Propris Alice Di Rocco Arianna Di Rocco Sabina Chiaretti Alex Moretti Sara Napolitano Maurizio Martelli Adriana Balduzzi Giuseppe Gaipa Andrea Biondi Robin Foà Long-Term Host Immune Modulation Following Tisagenlecleucel Administration in Patients with Diffuse Large B-Cell Lymphoma and B-Lineage Acute Lymphoblastic Leukemia Cancers CAR-T cells DLBCL B-ALL immune modulation |
| title | Long-Term Host Immune Modulation Following Tisagenlecleucel Administration in Patients with Diffuse Large B-Cell Lymphoma and B-Lineage Acute Lymphoblastic Leukemia |
| title_full | Long-Term Host Immune Modulation Following Tisagenlecleucel Administration in Patients with Diffuse Large B-Cell Lymphoma and B-Lineage Acute Lymphoblastic Leukemia |
| title_fullStr | Long-Term Host Immune Modulation Following Tisagenlecleucel Administration in Patients with Diffuse Large B-Cell Lymphoma and B-Lineage Acute Lymphoblastic Leukemia |
| title_full_unstemmed | Long-Term Host Immune Modulation Following Tisagenlecleucel Administration in Patients with Diffuse Large B-Cell Lymphoma and B-Lineage Acute Lymphoblastic Leukemia |
| title_short | Long-Term Host Immune Modulation Following Tisagenlecleucel Administration in Patients with Diffuse Large B-Cell Lymphoma and B-Lineage Acute Lymphoblastic Leukemia |
| title_sort | long term host immune modulation following tisagenlecleucel administration in patients with diffuse large b cell lymphoma and b lineage acute lymphoblastic leukemia |
| topic | CAR-T cells DLBCL B-ALL immune modulation |
| url | https://www.mdpi.com/2072-6694/15/9/2411 |
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