GÉTICA 2021

49 [ F I T C á n c e r - 7 ] Background: Sarcomas are heterogeneous and clinically challenging cancers that re- present 12-15 % of pediatric tumors. Current treatments are resulting in modest outcomes for patients with sarcoma. Therefore, innova- tive therapies are crucial to increase survival and improve the quality of life of these chil- dren and young adults. Natural Killer (NK) cells recognize and eli- minate malignant cells without the need of prior sensitization. Previous results from our group unveiled anti-tumor capacities of NK cells through their activating receptor NKG2D, whose ligands are often overexpres- sed in sarcoma cells. Also, we proved that autologous and allogenic NK cell adoptive transfer is feasible and safe in large-scale clinical trials. Nevertheless, their limited per- sistence and the immunosuppressive tumor microenvironment (TME) dampen NK-based immunotherapy efficacy in solid tumors, making a requirement for ground-breaking approaches to ameliorate NK cell anti-tumor functionality. Cytokine-induced memory-like (CIML) NK cells have been recently described as briefly pre-activated NK cells displaying leading pro- perties that include enhanced proliferation, expression of IL-2R, and increased IFN? pro- duction. Notably, Romee R. and collaborators uncovered CIML-NK cell responses to cancer CC-11. MEMORY-LIKE NK CELLS: A NOVEL THERAPY FOR PEDIATRIC SARCOMA Martín Cortázar, Carla; Navarro Zapata, Alfonso; Mestre Durán, Carmen; Clares Villa, Laura; Al Akioui, Karima; Ferreras, Cristina; Pérez Martínez, Antonio Instituto de Investigación IdiPAZ. Hospital Universitario La Paz. Madrid targets with magnificent outcomes in acute myeloid leukemia patients. Moreover, other studies reported that ML-NK cells exhibit long- term survival and in vivo persistence, and re- sistance to the TME. Objectives: Characterizing in depth CIML-NK cells and exploring their potential cytotoxic activity against sarcoma cells. Methods: To generate CIML-NK cells, highly purified NK cells were obtained from heal- thy donors and pre-activated with cytokine cocktail. Cells were maintained 6 days for ML-differentiation. Their degranulation ca- pacity and cytokine production facing sarco- ma cells were evaluated by flow cytometry. Cytotoxic potential of CIML-NK cells against sarcoma targets was studied by lactate de- hydrogenase (LDH) assays. Also, differential expression of CIML-NK receptors was charac- terized. Results: CIML-NK cells exhibited a phenoty- pe characterized by high expression of CD25, CD57, NKG2C and DNAM-1 among other mar- kers. When co-cultured with sarcoma cells, CIML-NK cells showed an increased IFN? pro- duction but non-significant differences were found in CD107a expression as compared to controls. LDH-cytotoxicity assays did not un- veil significant differences when comparing CIML- and control-NK cells.