Human natural killer cells: news in the therapy of solid tumors and high-risk leukemias

G. Pietra, C. Vitale, D. Pende, A. Bertaina, Francesca Moretta, M. Falco, P. Vacca, E. Montaldo, C. Cantoni, M.C. Mingari, A. Moretta, F. Locatelli, L. Moretta

Research output: Contribution to journalArticle

Abstract

It is well established that natural killer (NK) cells play an important role in the immunity against cancer, while the involvement of other recently identified, NK-related innate lymphoid cells is still poorly defined. In the haploidentical hematopoietic stem cell transplantation for the therapy of high-risk leukemias, NK cells have been shown to exert a key role in killing leukemic blasts residual after conditioning. While the clinical results in the cure of leukemias are excellent, the exploitation of NK cells in the therapy of solid tumors is still limited and unsatisfactory. In solid tumors, NK cell function may be inhibited via different mechanisms, occurring primarily at the tumor site. The cellular interactions in the tumor microenvironment involve tumor cells, stromal cells and resident or recruited leukocytes and may favor tumor evasion from the host’s defenses. In this context, a number of cytokines, growth factors and enzymes synthesized by tumor cells, stromal cells, suppressive/regulatory myeloid and lymphoid cells may substantially impair the function of different tumor-reactive effector cells, including NK cells. The identification and characterization of such mechanisms may offer clues for the development of new immunotherapeutic strategies to restore effective anti-tumor responses. In order to harness NK cell-based immunotherapies, several approaches have been proposed, including reinforcement of NK cell cytotoxicity by means of specific cytokines, antibodies or drugs. These new tools may improve NK cell function and/or increase tumor susceptibility to NK-mediated killing. Hence, the integration of NK-based immunotherapies with conventional anti-tumor therapies may increase chances of successful cancer treatment. © 2015, Springer-Verlag Berlin Heidelberg.
Original languageEnglish
Pages (from-to)465-476
Number of pages12
JournalCancer Immunology and Immunotherapy
Volume65
Issue number4
DOIs
Publication statusPublished - 2016

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Natural Killer Cells
Leukemia
Neoplasms
Therapeutics
Stromal Cells
Cell- and Tissue-Based Therapy
Immunotherapy
Lymphocytes
Cytokines
Tumor Microenvironment
Hematopoietic Stem Cell Transplantation
Berlin
Myeloid Cells
Immunity
Intercellular Signaling Peptides and Proteins
Leukocytes
Antibodies

Keywords

  • Acute leukemias
  • Hematopoietic stem cell transplantation
  • Immunotherapy
  • Innate lymphoid cells
  • NK cells
  • Tumor microenvironment
  • adoptive immunotherapy
  • biological model
  • cell communication
  • cytotoxicity
  • hematopoietic stem cell transplantation
  • human
  • immunology
  • leukemia
  • natural killer cell
  • Neoplasms
  • procedures
  • transplantation
  • tumor microenvironment
  • Cell Communication
  • Cytotoxicity, Immunologic
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunotherapy, Adoptive
  • Killer Cells, Natural
  • Leukemia
  • Models, Immunological
  • Tumor Microenvironment

Cite this

Human natural killer cells: news in the therapy of solid tumors and high-risk leukemias. / Pietra, G.; Vitale, C.; Pende, D.; Bertaina, A.; Moretta, Francesca; Falco, M.; Vacca, P.; Montaldo, E.; Cantoni, C.; Mingari, M.C.; Moretta, A.; Locatelli, F.; Moretta, L.

In: Cancer Immunology and Immunotherapy, Vol. 65, No. 4, 2016, p. 465-476.

Research output: Contribution to journalArticle

Pietra, G, Vitale, C, Pende, D, Bertaina, A, Moretta, F, Falco, M, Vacca, P, Montaldo, E, Cantoni, C, Mingari, MC, Moretta, A, Locatelli, F & Moretta, L 2016, 'Human natural killer cells: news in the therapy of solid tumors and high-risk leukemias', Cancer Immunology and Immunotherapy, vol. 65, no. 4, pp. 465-476. https://doi.org/10.1007/s00262-015-1744-y
Pietra, G. ; Vitale, C. ; Pende, D. ; Bertaina, A. ; Moretta, Francesca ; Falco, M. ; Vacca, P. ; Montaldo, E. ; Cantoni, C. ; Mingari, M.C. ; Moretta, A. ; Locatelli, F. ; Moretta, L. / Human natural killer cells: news in the therapy of solid tumors and high-risk leukemias. In: Cancer Immunology and Immunotherapy. 2016 ; Vol. 65, No. 4. pp. 465-476.
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title = "Human natural killer cells: news in the therapy of solid tumors and high-risk leukemias",
abstract = "It is well established that natural killer (NK) cells play an important role in the immunity against cancer, while the involvement of other recently identified, NK-related innate lymphoid cells is still poorly defined. In the haploidentical hematopoietic stem cell transplantation for the therapy of high-risk leukemias, NK cells have been shown to exert a key role in killing leukemic blasts residual after conditioning. While the clinical results in the cure of leukemias are excellent, the exploitation of NK cells in the therapy of solid tumors is still limited and unsatisfactory. In solid tumors, NK cell function may be inhibited via different mechanisms, occurring primarily at the tumor site. The cellular interactions in the tumor microenvironment involve tumor cells, stromal cells and resident or recruited leukocytes and may favor tumor evasion from the host’s defenses. In this context, a number of cytokines, growth factors and enzymes synthesized by tumor cells, stromal cells, suppressive/regulatory myeloid and lymphoid cells may substantially impair the function of different tumor-reactive effector cells, including NK cells. The identification and characterization of such mechanisms may offer clues for the development of new immunotherapeutic strategies to restore effective anti-tumor responses. In order to harness NK cell-based immunotherapies, several approaches have been proposed, including reinforcement of NK cell cytotoxicity by means of specific cytokines, antibodies or drugs. These new tools may improve NK cell function and/or increase tumor susceptibility to NK-mediated killing. Hence, the integration of NK-based immunotherapies with conventional anti-tumor therapies may increase chances of successful cancer treatment. {\circledC} 2015, Springer-Verlag Berlin Heidelberg.",
keywords = "Acute leukemias, Hematopoietic stem cell transplantation, Immunotherapy, Innate lymphoid cells, NK cells, Tumor microenvironment, adoptive immunotherapy, biological model, cell communication, cytotoxicity, hematopoietic stem cell transplantation, human, immunology, leukemia, natural killer cell, Neoplasms, procedures, transplantation, tumor microenvironment, Cell Communication, Cytotoxicity, Immunologic, Hematopoietic Stem Cell Transplantation, Humans, Immunotherapy, Adoptive, Killer Cells, Natural, Leukemia, Models, Immunological, Tumor Microenvironment",
author = "G. Pietra and C. Vitale and D. Pende and A. Bertaina and Francesca Moretta and M. Falco and P. Vacca and E. Montaldo and C. Cantoni and M.C. Mingari and A. Moretta and F. Locatelli and L. Moretta",
note = "Cited By :3 Export Date: 31 March 2017 CODEN: CIIMD Correspondence Address: Moretta, L.; IRCCS Ospedale Pediatrico Bambino Ges{\`u}Italy; email: lorenzomoretta@opbg.net References: Vivier, E., Raulet, D.H., Moretta, A., Caligiuri, M.A., Zitvogel, L., Lanier, L.L., Yokoyama, W.M., Ugolini, S., Innate or adaptive immunity? 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year = "2016",
doi = "10.1007/s00262-015-1744-y",
language = "English",
volume = "65",
pages = "465--476",
journal = "Cancer Immunology and Immunotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "4",

}

TY - JOUR

T1 - Human natural killer cells: news in the therapy of solid tumors and high-risk leukemias

AU - Pietra, G.

AU - Vitale, C.

AU - Pende, D.

AU - Bertaina, A.

AU - Moretta, Francesca

AU - Falco, M.

AU - Vacca, P.

AU - Montaldo, E.

AU - Cantoni, C.

AU - Mingari, M.C.

AU - Moretta, A.

AU - Locatelli, F.

AU - Moretta, L.

N1 - Cited By :3 Export Date: 31 March 2017 CODEN: CIIMD Correspondence Address: Moretta, L.; IRCCS Ospedale Pediatrico Bambino GesùItaly; email: lorenzomoretta@opbg.net References: Vivier, E., Raulet, D.H., Moretta, A., Caligiuri, M.A., Zitvogel, L., Lanier, L.L., Yokoyama, W.M., Ugolini, S., Innate or adaptive immunity? 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PY - 2016

Y1 - 2016

N2 - It is well established that natural killer (NK) cells play an important role in the immunity against cancer, while the involvement of other recently identified, NK-related innate lymphoid cells is still poorly defined. In the haploidentical hematopoietic stem cell transplantation for the therapy of high-risk leukemias, NK cells have been shown to exert a key role in killing leukemic blasts residual after conditioning. While the clinical results in the cure of leukemias are excellent, the exploitation of NK cells in the therapy of solid tumors is still limited and unsatisfactory. In solid tumors, NK cell function may be inhibited via different mechanisms, occurring primarily at the tumor site. The cellular interactions in the tumor microenvironment involve tumor cells, stromal cells and resident or recruited leukocytes and may favor tumor evasion from the host’s defenses. In this context, a number of cytokines, growth factors and enzymes synthesized by tumor cells, stromal cells, suppressive/regulatory myeloid and lymphoid cells may substantially impair the function of different tumor-reactive effector cells, including NK cells. The identification and characterization of such mechanisms may offer clues for the development of new immunotherapeutic strategies to restore effective anti-tumor responses. In order to harness NK cell-based immunotherapies, several approaches have been proposed, including reinforcement of NK cell cytotoxicity by means of specific cytokines, antibodies or drugs. These new tools may improve NK cell function and/or increase tumor susceptibility to NK-mediated killing. Hence, the integration of NK-based immunotherapies with conventional anti-tumor therapies may increase chances of successful cancer treatment. © 2015, Springer-Verlag Berlin Heidelberg.

AB - It is well established that natural killer (NK) cells play an important role in the immunity against cancer, while the involvement of other recently identified, NK-related innate lymphoid cells is still poorly defined. In the haploidentical hematopoietic stem cell transplantation for the therapy of high-risk leukemias, NK cells have been shown to exert a key role in killing leukemic blasts residual after conditioning. While the clinical results in the cure of leukemias are excellent, the exploitation of NK cells in the therapy of solid tumors is still limited and unsatisfactory. In solid tumors, NK cell function may be inhibited via different mechanisms, occurring primarily at the tumor site. The cellular interactions in the tumor microenvironment involve tumor cells, stromal cells and resident or recruited leukocytes and may favor tumor evasion from the host’s defenses. In this context, a number of cytokines, growth factors and enzymes synthesized by tumor cells, stromal cells, suppressive/regulatory myeloid and lymphoid cells may substantially impair the function of different tumor-reactive effector cells, including NK cells. The identification and characterization of such mechanisms may offer clues for the development of new immunotherapeutic strategies to restore effective anti-tumor responses. In order to harness NK cell-based immunotherapies, several approaches have been proposed, including reinforcement of NK cell cytotoxicity by means of specific cytokines, antibodies or drugs. These new tools may improve NK cell function and/or increase tumor susceptibility to NK-mediated killing. Hence, the integration of NK-based immunotherapies with conventional anti-tumor therapies may increase chances of successful cancer treatment. © 2015, Springer-Verlag Berlin Heidelberg.

KW - Acute leukemias

KW - Hematopoietic stem cell transplantation

KW - Immunotherapy

KW - Innate lymphoid cells

KW - NK cells

KW - Tumor microenvironment

KW - adoptive immunotherapy

KW - biological model

KW - cell communication

KW - cytotoxicity

KW - hematopoietic stem cell transplantation

KW - human

KW - immunology

KW - leukemia

KW - natural killer cell

KW - Neoplasms

KW - procedures

KW - transplantation

KW - tumor microenvironment

KW - Cell Communication

KW - Cytotoxicity, Immunologic

KW - Hematopoietic Stem Cell Transplantation

KW - Humans

KW - Immunotherapy, Adoptive

KW - Killer Cells, Natural

KW - Leukemia

KW - Models, Immunological

KW - Tumor Microenvironment

U2 - 10.1007/s00262-015-1744-y

DO - 10.1007/s00262-015-1744-y

M3 - Article

VL - 65

SP - 465

EP - 476

JO - Cancer Immunology and Immunotherapy

JF - Cancer Immunology and Immunotherapy

SN - 0340-7004

IS - 4

ER -