Page 165 - Haematologica August 2018

Unconventional CD56dim/CD16neg NK cells in HSCT
plant. Indeed, the blocking of CD94/NKG2A with a mask- ing mAb significantly increased the CD107a degranula- tion as a marker of lytic activity of NK cells purified early after hHSCT. Although the mechanism(s) inducing the expansion of anergic NKG2Apos/uCD56dim NK cells is unknown, this acquired knowledge now makes it possible to develop a therapeutic approach targeting a specific immune check-point whose inhibition can efficiently increase NK cell alloreactivity within a given time-frame after hHSCT. In this regard, the efficacy of the in vivo administration of an anti-CD94/NKG2A blocking mAb (i.e., Monalizumab) in improving NK cell cytotoxicity against solid tumors and leukemic cells has been already reported both in mice and humans.44,45 (clinicaltrials.gov Identifier: 02459301) (Figure 8).
Acknowledgments
The authors thank the patients for their generosity and partic- ipation in this study and the nurses of the Hematology and Bone Marrow Transplant Unit (Humanitas Clinical and Research
Center). The present study is dedicated to the memory of Alessandro Moretta, a great mentor and a pillar in the field of NK cell biology.
Funding
This work was supported by Fondazione Cariplo (Grant per la Ricerca Biomedica 2012/0683 to EL and 2015/0603 to DM), Associazione Italiana per la Ricerca sul Cancro (MFAG 10607 to EL, IG.20312 to EM and IG 14687 to DM), by the Italian Ministry of Health (Bando Giovani Ricercatori GR-2011- 02347324 to EL and GR-2013-02356522 to AR), the intramu- ral program of the National Institutes of Allergy and Infectious Diseases (to MR) and intramural research and clinical funding programs of Humanitas Research Hospital (to DM and LC). AR is a recipient of the Guglielmina Lucatello e Gino Mazzega fel- lowship from the Fondazione Italiana per la Ricerca sul Cancro. EZ is a recipient of the Nella Orlandini fellowship from the Fondazione Italiana per la Ricerca sul Cancro. CDV and EMCM are recipients of post-doctoral fellowships from the Fondazione Umberto Veronesi.
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