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
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.
