Mucosal-associated invariant T cells are functionally impaired in pediatric and young adult patients following allogeneic hematopoietic stem cell transplantation and their recovery correlates with clinical outcomes

Federica Galaverna; Sara Flamini; Carmen Dolores De Luca; Ilaria Pili; Emilia Boccieri; Francesca Benini; Francesco Quagliarella; Chiara Rosignoli; Marco Rosichini; Shirley Genah; Marialuigia Catanoso; Antonella Cardinale; Gabriele Volpe; Marianna Coccetti; Angela Pitisci; Giuseppina Li Pira; Roberto Carta; Barbarella Lucarelli; Francesca Del Bufalo; Valentina Bertaina; Marco Becilli; Daria Pagliara; Mattia Algeri; Pietro Merli; Franco Locatelli; Enrico Velardi

doi:10.3324/haematol.2023.284649

Haematologica (May 2024)

Mucosal-associated invariant T cells are functionally impaired in pediatric and young adult patients following allogeneic hematopoietic stem cell transplantation and their recovery correlates with clinical outcomes

Federica Galaverna,
Sara Flamini,
Carmen Dolores De Luca,
Ilaria Pili,
Emilia Boccieri,
Francesca Benini,
Francesco Quagliarella,
Chiara Rosignoli,
Marco Rosichini,
Shirley Genah,
Marialuigia Catanoso,
Antonella Cardinale,
Gabriele Volpe,
Marianna Coccetti,
Angela Pitisci,
Giuseppina Li Pira,
Roberto Carta,
Barbarella Lucarelli,
Francesca Del Bufalo,
Valentina Bertaina,
Marco Becilli,
Daria Pagliara,
Mattia Algeri,
Pietro Merli,
Franco Locatelli,
Enrico Velardi

Affiliations

Federica Galaverna: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Sara Flamini: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Carmen Dolores De Luca: Department of Maternal and Child Health, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome
Ilaria Pili: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Emilia Boccieri: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Francesca Benini: Department of Maternal and Child Health, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome
Francesco Quagliarella: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Chiara Rosignoli: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Marco Rosichini: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161 Rome
Shirley Genah: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Marialuigia Catanoso: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Antonella Cardinale: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Gabriele Volpe: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Marianna Coccetti: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Angela Pitisci: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Giuseppina Li Pira: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Roberto Carta: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Barbarella Lucarelli: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Francesca Del Bufalo: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Valentina Bertaina: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Marco Becilli: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Daria Pagliara: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Mattia Algeri: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; Department of Health Sciences, Magna Graecia University, Catanzaro
Pietro Merli: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome
Franco Locatelli: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; Department of Maternal and Child Health, Catholic University of the Sacred Heart, Largo Francesco Vito, 1, 00168 Rome
Enrico Velardi: Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome

DOI: https://doi.org/10.3324/haematol.2023.284649
Journal volume & issue: Vol. 999, no. 1

Abstract

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Mucosal-associated invariant T (MAIT) cells are innate-like T-cells implicated in the response to fungal and bacterial infections. Their contribution to restoring T-cell immunity and influencing hematopoietic stem cell transplant (HSCT) outcomes remains poorly understood. We retrospectively studied MAIT-cell recovery in 145 consecutive children and young adults with hematological malignancies undergoing allo-HSCT, between April/2019 and May/2022, from unrelated matched donor (MUD, n=52), with standard graft-versus-host-disease (GvHD) prophylaxis, or HLA-haploidentical (Haplo, n=93) donor after in vitro αβT/CD19-cell depletion, without post-HSCT pharmacological prophylaxis. With a median follow-up of 33 months (12-49), overall survival (OS), disease-free survival (DFS) and non-relapse mortality (NRM) were 79.5%, 72% and 7%, respectively; GvHD-free, Relapse-free Survival (GRFS) was 63%, while cumulative incidence of relapse was 23%. While WWT-cells reconstituted 1-2 years post-HSCT, MAIT-cells showed delayed recovery and prolonged functional impairment, characterized by expression of activation (CD25, CD38), exhaustion (PD1, TIM3) and senescence (CD57) markers, and suboptimal ex vivo response. OS, DFS and NRM were not affected by MAIT-cells. Interestingly, higher MAIT-cells at day+30 correlated with higher incidence of grade II-IV acute GvHD (19% vs 7%, p=0.06). Furthermore, a greater MAIT-cell count tended to be associated with a higher incidence of chronic GvHD (17% vs 6%, p=0.07) resulting in lower GRFS (55% vs 73%, p=0.05). Higher MAIT-cells also correlated with greater cytomegalovirus (CMV) reactivation and lower late blood stream infections (BSI) (44% vs 24%, p=0.02 and 9% vs 18%, p=0.08, respectively). Future studies are needed to confirm the impact of early MAIT-cell recovery on cGvHD, CMV reactivation and late BSI.

Published in Haematologica

ISSN: 0390-6078 (Print); 1592-8721 (Online)
Publisher: Ferrata Storti Foundation
Country of publisher: Italy
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the blood and blood-forming organs
Website: http://www.haematologica.org

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