Abstract
Natural Killer cells (NK) are innate effector cells with a critical role in immunosurveillance against different kinds of cancer cells, including Multiple Myeloma (MM). However, the number and/or function of these lymphocytes are strongly reduced during MM progression and in advanced clinical stages. A better understanding of the mechanisms controlling both MM and NK cell biology have greatly contributed to develop novel and combined therapeutic strategies in the treatment of this incurable hematologic malignancy. These include approaches to reverse the immunosuppressive MM microenvironment or potentiate the natural or antibody-dependent cellular cytotoxicity (ADCC) of NK cells. Moreover, chemotherapeutic drugs or specific monoclonal antibodies (mAbs) can render cancer cells more susceptible to NK cell-mediated recognition and lysis; direct enhancement of NK cell function can be obtained by means of immunomodulatory drugs, cytokines and blocking mAbs targeting NK cell inhibitory receptors. Finally, adoptive transfer of ex-vivo expanded and genetically manipulated NK cells is also a promising therapeutic tool for MM. Here, we review current knowledge on complex mechanisms affecting NK cell activity during MM progression. We also discuss recent advances on innovative approaches aimed at boosting the functions of these cytotoxic innate lymphocytes. In particular, we focus our attention on recent preclinical and clinical studies addressing the therapeutic potential of different NK cell-based strategies for the management of MM.
| Original language | English |
|---|---|
| Pages (from-to) | 255-264 |
| Number of pages | 10 |
| Journal | Cancer Treatment Reviews |
| Volume | 70 |
| DOIs | |
| Publication status | Published - Nov 1 2018 |
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Keywords
- Immunotherapy
- Multiple myeloma
- NK cells
ASJC Scopus subject areas
- Oncology
- Radiology Nuclear Medicine and imaging
Cite this
Translating the anti-myeloma activity of Natural Killer cells into clinical application. / Fionda, Cinzia; Stabile, Helena; Molfetta, Rosa; Soriani, Alessandra; Bernardini, Giovanni; Zingoni, Alessandra; Gismondi, Angela; Paolini, Rossella; Cippitelli, Marco; Santoni, Angela.
In: Cancer Treatment Reviews, Vol. 70, 01.11.2018, p. 255-264.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Translating the anti-myeloma activity of Natural Killer cells into clinical application
AU - Fionda, Cinzia
AU - Stabile, Helena
AU - Molfetta, Rosa
AU - Soriani, Alessandra
AU - Bernardini, Giovanni
AU - Zingoni, Alessandra
AU - Gismondi, Angela
AU - Paolini, Rossella
AU - Cippitelli, Marco
AU - Santoni, Angela
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Natural Killer cells (NK) are innate effector cells with a critical role in immunosurveillance against different kinds of cancer cells, including Multiple Myeloma (MM). However, the number and/or function of these lymphocytes are strongly reduced during MM progression and in advanced clinical stages. A better understanding of the mechanisms controlling both MM and NK cell biology have greatly contributed to develop novel and combined therapeutic strategies in the treatment of this incurable hematologic malignancy. These include approaches to reverse the immunosuppressive MM microenvironment or potentiate the natural or antibody-dependent cellular cytotoxicity (ADCC) of NK cells. Moreover, chemotherapeutic drugs or specific monoclonal antibodies (mAbs) can render cancer cells more susceptible to NK cell-mediated recognition and lysis; direct enhancement of NK cell function can be obtained by means of immunomodulatory drugs, cytokines and blocking mAbs targeting NK cell inhibitory receptors. Finally, adoptive transfer of ex-vivo expanded and genetically manipulated NK cells is also a promising therapeutic tool for MM. Here, we review current knowledge on complex mechanisms affecting NK cell activity during MM progression. We also discuss recent advances on innovative approaches aimed at boosting the functions of these cytotoxic innate lymphocytes. In particular, we focus our attention on recent preclinical and clinical studies addressing the therapeutic potential of different NK cell-based strategies for the management of MM.
AB - Natural Killer cells (NK) are innate effector cells with a critical role in immunosurveillance against different kinds of cancer cells, including Multiple Myeloma (MM). However, the number and/or function of these lymphocytes are strongly reduced during MM progression and in advanced clinical stages. A better understanding of the mechanisms controlling both MM and NK cell biology have greatly contributed to develop novel and combined therapeutic strategies in the treatment of this incurable hematologic malignancy. These include approaches to reverse the immunosuppressive MM microenvironment or potentiate the natural or antibody-dependent cellular cytotoxicity (ADCC) of NK cells. Moreover, chemotherapeutic drugs or specific monoclonal antibodies (mAbs) can render cancer cells more susceptible to NK cell-mediated recognition and lysis; direct enhancement of NK cell function can be obtained by means of immunomodulatory drugs, cytokines and blocking mAbs targeting NK cell inhibitory receptors. Finally, adoptive transfer of ex-vivo expanded and genetically manipulated NK cells is also a promising therapeutic tool for MM. Here, we review current knowledge on complex mechanisms affecting NK cell activity during MM progression. We also discuss recent advances on innovative approaches aimed at boosting the functions of these cytotoxic innate lymphocytes. In particular, we focus our attention on recent preclinical and clinical studies addressing the therapeutic potential of different NK cell-based strategies for the management of MM.
KW - Immunotherapy
KW - Multiple myeloma
KW - NK cells
UR - http://www.scopus.com/inward/record.url?scp=85054654749&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054654749&partnerID=8YFLogxK
U2 - 10.1016/j.ctrv.2018.10.005
DO - 10.1016/j.ctrv.2018.10.005
M3 - Review article
C2 - 30326421
AN - SCOPUS:85054654749
VL - 70
SP - 255
EP - 264
JO - Cancer Treatment Reviews
JF - Cancer Treatment Reviews
SN - 0305-7372
ER -