γδ T-Cells

 

γδT-Cells are a subset of CD3+ cells combining conventional adaptive features with rapid, innate-like responses that place them in the initiation phase of immune reactions. In addition, they recognize tumor cells without recourse to the classical major histocompatibility complex (MHC) presentation.

Here, in the Bertaina Laboratory, we believe that post-HSCT infusions of γδ T-cells could reduce the risk of relapse and improve immune reconstitution in leukemia patients. To this end, our goal is to establish a new protocol for the ex vivo expansion of γδ T-cells.

We are performing the expansion of γδ T cells using different strategies. We will characterize these cells both phenotypically and functionally in order to uncover the optimal strategy for the translational purposes mentioned above. Moreover, we want to have a better understanding of the mechanism of action of this unique T-cell subset. We will exploit cutting edges techniques that only Stanford University has to offer for understanding the mechanism of γδ T-Cells interactions with leukemic cells.

  • References:
  • 1.  Bertaina A, Merli P, Rutella S, Pagliara D, Bernardo ME, Masetti R, Pende D, Falco M, Handgretinger R, Moretta F, Lucarelli B, Brescia LP, Li Pira G, Testi M, Cancrini C, Kabbara N, Carsetti R, Finocchi A, Moretta A, Moretta L, Locatelli F. HLA-haploidentical stem cell transplantation after removal of αβ+ T and B cells in children with nonmalignant disorders.Blood. 2014 Jul 31;124(5):822-6. doi: 10.1182/blood-2014-03-563817. Epub 2014 May 28.
  • 2.  Airoldi I, Bertaina A, Prigione I, Zorzoli A, Pagliara D, Cocco C, Meazza R, Loiacono F, Lucarelli B, Bernardo ME, Barbarito G, Pende D, Moretta A, Pistoia V, Moretta L, Locatelli F. Blood.  γδ T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-αβ+/CD19+ lymphocytes. 2015 Apr 9;125(15):2349-58. doi: 10.1182/blood-2014-09-599423. Epub 2015 Jan 22. Erratum in: Blood. 2016 Mar 24;127(12):1620.
  • 3. Bertaina A, Zorzoli A, Petretto A, Barbarito G, Inglese E, Merli P, Lavarello C, Brescia LP, De Angelis B, Tripodi G, Moretta L, Locatelli F, Airoldi I. Zoledronic acid boosts γδ T-cell activity in children receiving αβ+ T and CD19+ cell-depleted grafts from an HLA-haplo-identical donor. Oncoimmunology. 2016 Sep 27;6(2):e1216291. doi: 10.1080/2162402X.2016.1216291. eCollection 2017.
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In the presence of ZOL and IL-2, γδ T cells consistently expanded in vitro from PBMC and this population was Vγ9Vδ2 (panels b-d).

 

CD107a expression was investigated in gated Vd2 γδ T-cells, cultured with ALL or AML blasts untreated (T) or after ZOL-exposure (T+ZOL). Analyses were performed in PBMC from patients before (pre), after the first (post I) and the third or fifth (post III/V) ZOL infusion (a). Comparative analyses of Vd2 γδ T-cells (gated in CD3+ γδ+T cells) performed by flow cytometry, in patients receiving two ZOL infusions and that died versus those that were alive at the end of the study (b). Functionally grouped network that visualizes the non-redundant biological terms of GOMF and KEGG derived by a Fischer’s Exact Test, on protein significantly modulated in γδ T cells circulating in transplanted patients after the first ZOL treatment. Red circles represent the upregulated pathways, whereas the blue circles those downregulated (c).