Natural Killer Cells as an Immune Cell Therapy Option for Bone Marrow Transplantation in Hematological Malignancies: Implications for New Therapies Based on Lipid Transfer and Cell-to- Cell Communication
Pp. 132-175 (44)
Beatriz Martín-Antonio, Nuria Martínez-Cibrian, Alvaro Urbano- Ispizua and Ciril Rozman
Natural killer (NK) cells belong to the innate immune system. In recent years it
has been suggested that their use could improve the outcome of stem cell transplantation
for hematological malignancies, mainly due to the high anti-tumor effect they mediate and
because they are not associated with an increase of the graft versus host disease, a
complication which decreases the survival of patients submitted to this procedure. Once
activated by several mechanisms, NK cells deliver cytolytic molecules triggering different
cell death pathways, which can be caspase-3 dependent or caspase-3 independent, such as
endoplasmic reticulum stress or lysosomal cell death. Apparently, NK cells take advantage
of the particular features of different tumor cells to attack them in a more efficient way.
Understanding the factors that contribute to cancer cell death is therefore critical for the
development of novel therapies and to circumvent chemo-resistance.
Lipids are emerging as new targets for anti-inflammatory and cancer therapies as they
interact extensively with organelles, are involved in immune responses, and can lead to
initiation of different types of cell death. Interactions between lipids with membranes
are crucial for the effects they mediate in cell-to-cell communication. Our group
demonstrated that cord blood derived NK cells (CB-NK) can be efficiently expanded in
vitro and exert anti-tumor activity both in vitro and in vivo in a multiple myeloma (MM)
model thus, providing a clinically applicable strategy for the generation of highly
functional NK cells which can be used to eradicate this and potentially other
hematological malignancies. Our group also showed that CB-NK mediate a specific
tumor cell death against MM which is transmissible between cells, and where lipidprotein
vesicle trafficking play a relevant role. These findings provide the rationale for
the development of CB-NK based therapeutic strategies in the treatment of
In this paper, the strengths and the weaknesses of clinical trials using NK cells are
discussed. In addition, some guidelines for the development of future trials are
Stem cell transplantation (SCT), natural killer (NK) cells, cell death,
lipids, cell-to-cell communication, autophagy, multiple myeloma (MM).
Department of Hematology, Hospital Clinic, IDIBAPS, Barcelona, Spain; Josep Carreras Leukaemia Research Institute, Barcelona, Spain.