Background: 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). Methods: 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. Results: 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+, CD4+, CD8+, and NK cells over time, as well as a decrease in Treg cells, and an increased IFNγ and TNFα production by T lymphocytes. Conclusions: 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.

Long-term host immune modulation following tisagenlecleucel administration in patients with diffuse large b-cell lymphoma and b-lineage acute lymphoblastic leukemia / Guarini, Anna; Radice, Giulia; Peragine, Nadia; Buracchi, Chiara; De Propris, Maria Stefania; Di Rocco, Alice; Di Rocco, Arianna; Chiaretti, Sabina; Moretti, Alex; Napolitano, Sara; Martelli, Maurizio; Balduzzi, Adriana; Gaipa, Giuseppe; Biondi, Andrea; Foà, Robin. - In: CANCERS. - ISSN 2072-6694. - 15:9(2023), pp. 1-13. [10.3390/cancers15092411]

Long-term host immune modulation following tisagenlecleucel administration in patients with diffuse large b-cell lymphoma and b-lineage acute lymphoblastic leukemia

Guarini, Anna;Radice, Giulia;Peragine, Nadia;De Propris, Maria Stefania;Di Rocco, Alice;Di Rocco, Arianna;Chiaretti, Sabina;Martelli, Maurizio;Foà, Robin
2023

Abstract

Background: 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). Methods: 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. Results: 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+, CD4+, CD8+, and NK cells over time, as well as a decrease in Treg cells, and an increased IFNγ and TNFα production by T lymphocytes. Conclusions: 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.
2023
b-all; car-t cells; dlbcl; immune modulation
01 Pubblicazione su rivista::01a Articolo in rivista
Long-term host immune modulation following tisagenlecleucel administration in patients with diffuse large b-cell lymphoma and b-lineage acute lymphoblastic leukemia / Guarini, Anna; Radice, Giulia; Peragine, Nadia; Buracchi, Chiara; De Propris, Maria Stefania; Di Rocco, Alice; Di Rocco, Arianna; Chiaretti, Sabina; Moretti, Alex; Napolitano, Sara; Martelli, Maurizio; Balduzzi, Adriana; Gaipa, Giuseppe; Biondi, Andrea; Foà, Robin. - In: CANCERS. - ISSN 2072-6694. - 15:9(2023), pp. 1-13. [10.3390/cancers15092411]
File allegati a questo prodotto
File Dimensione Formato  
Guarini_Long-term_2023.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 1.24 MB
Formato Adobe PDF
1.24 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1680679
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 2
social impact