Poject_NK cell ontogenesis

Targeting NK cell ontogenesis and homeostasis to disclose the mechanisms inducing the onset of hematologic malignancies

The Bone Marrow (BM) niche is a major site for the prelude of human Natural Killer (NK) cell ontogenesis. Hereupon, NK cell precursors (NKPs) enter the Peripheral Blood (PB) to differentiate into terminally differentiated cytokine producer and cytotoxic NK cells. While the characteristics and functions of mature NK cell subsets have grown, the NK cell-poiesis remains undetermined. In this project we are approaching NK cell ontogenesis at multiple layers:

Ex-vivo by setting up an autologous BM-niche co-culturing BM-derived stromal cells with FACS-sorted NKPs;
In-silico, through single cell RNA sequencing of BM and PB;
In-vivo by applying single-cell based pipelines to multi-parametric flow-cytometry data of NK cell immune reconstitution after hematopoietic stem cell transplantation, a model of NK cell differentiation.

TEAM

Clara Di Vito PhD - Senior staff scientist

Alessandro Frigo - Post-doctoral fellow

Lara Orlandi - PhD student

Paolo Marzano - PhD student, bioinformatician

Annalisa Imperiali - PhD student, bioinformatician

FUNDing

Associazione Italiana per la Ricerca sul Cancro (AIRC)

Project ID: IG 21567

Targeting allo-reactive Natural Killer cell immune reconstitution in hematologic tumors after bone marrow transplant

collaborations

Humanitas Cancer Center
IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy

Othopaedic Surgery Unit
IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy

related publications

Persistence of KIRneg NK cells after haploidentical hematopoietic stem cell transplantation protects from human cytomegalovirus infection/reactivation
Di Vito C, Coianiz N, Calvi M, Terzoli S, Zaghi E, Puccio S, Frigo A, Mariotti J, De Philippis C, Mannina D, Sarina B, Mineri R, Le-Trilling VTK, Trilling M, Castagna L, Bramanti S, Santoro A and Mavilio D.
Front. Immunol. 2024 Jan;14:1266051. doi: 10.3389/fimmu.2023.1266051.
Development of Human ILCs and Impact of Unconventional Cytotoxic Subsets in the Pathophysiology of Inflammatory Diseases and Cancer
Calvi M, Di Vito C, Frigo A, Trabanelli S, Jandus C, Mavilio D.
Front Immunol. 2022 May 26;13:914266. doi: 10.3389/fimmu.2022.914266.
Single-cell profiling identifies impaired adaptive NK cells expanded after HCMV reactivation in haploidentical HSCT
Zaghi E, Calvi M, Puccio S, Spata G, Terzoli S, Peano C, Roberto A, De Paoli F, van Beek JJ, Mariotti J, De Philippis C, Sarina B, Mineri R, Bramanti S, Santoro A, Le-Trilling VTK, Trilling M, Marcenaro E, Castagna L, Di Vito C, Lugli E, Mavilio D.
JCI Insight. 2021 Jun 22;6(12):e146973. doi: 10.1172/jci.insight.146973.
On the Way to Become a Natural Killer Cell
Di Vito C, Mikulak J, Mavilio D.
Front Immunol. 2019 Aug 2;10:1812. doi: 10.3389/fimmu.2019.01812.
Targeting NKG2A to elucidate natural killer cell ontogenesis and to develop novel immune-therapeutic strategies in cancer therapy
Zaghi E, Calvi M, Marcenaro E, Mavilio D, Di Vito C.
J Leukoc Biol. 2019 Jun;105(6):1243-1251. doi: 10.1002/JLB.MR0718-300R.
The early expansion of anergic NKG2Apos/CD56dim/CD16neg natural killer represents a therapeutic target in haploidentical hematopoietic stem cell transplantation
Roberto A, Di Vito C, Zaghi E, Mazza EMC, Capucetti A, Calvi M, Tentorio P, Zanon V, Sarina B, Mariotti J, Bramanti S, Tenedini E, Tagliafico E, Bicciato S, Santoro A, Roederer M, Marcenaro E, Castagna L, Lugli E, Mavilio D.
Haematologica. 2018 Aug;103(8):1390-1402. doi: 10.3324/haematol.2017.186619.