The role of natural killer cells in chronic myeloid leukemia

Danier, Anna Carolyna Araújo; Melo, Ricardo Pereira de; Napimoga, Marcelo Henrique; Laguna-Abreu, Maria Theresa Cerávolo

doi:10.5581/1516-8484.20110057

Cited by 9 publications

(10 citation statements)

References 42 publications

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“…Although without statistical significance, the expression of NKG2D was reduced in patients who relapsed. The activation of NKG2D induces the reactivity of NK cells against tumor cells [ 56 ], but the expression of this marker is negatively modulated in patients with CML and other types of cancer, which facilitates the escape of tumor cells [ 57 ]. However, treatment with TKIs modulated NKG2D expression, which would favor the lytic activity of NK cells [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Immunological Parameters as Predictive Biomarkers of Relapse in Patients with Chronic Myeloid Leukemia on Treatment-Free Remission

Vigón

Luna

Galán

et al. 2020

JCM

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BCR-ABL is an aberrant tyrosine kinase responsible for chronic myeloid leukemia (CML). Tyrosine kinase inhibitors (TKIs) induce a potent antileukemic response mostly based on the inhibition of BCR-ABL, but they also increase the activity of Natural Killer (NK) and CD8+ T cells. After several years, patients may interrupt treatment due to sustained, deep molecular response. By unknown reasons, half of the patients relapse during treatment interruption, whereas others maintain a potent control of the residual leukemic cells for several years. In this study, several immunological parameters related to sustained antileukemic control were analyzed. According to our results, the features more related to poor antileukemic control were as follows: low levels of cytotoxic cells such as NK, (Natural Killer T) NKT and CD8±TCRγβ+ T cells; low expression of activating receptors on the surface of NK and NKT cells; impaired synthesis of proinflammatory cytokines or proteases from NK cells; and HLA-E*0103 homozygosis and KIR haplotype BX. A Random Forest algorithm predicted 90% of the accuracy for the classification of CML patients in groups of relapse or non-relapse according to these parameters. Consequently, these features may be useful as biomarkers predictive of CML relapse in patients that are candidates to initiate treatment discontinuation.

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Section: Discussionmentioning

confidence: 99%

Identification of Immunological Parameters as Predictive Biomarkers of Relapse in Patients with Chronic Myeloid Leukemia on Treatment-Free Remission

Vigón

Luna

Galán

et al. 2020

JCM

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“…The aforementioned decrease of NK cell activating receptors may consequently cause an imbalance between activating and inactivating receptors and confer suppression of NK cell activity. Downregulation of receptor NKG2D or loss of the correlating ligands, is thought to contribute to immune escape of the leukemic clone by decreasing the NK cell mediated recognition of BCR-ABL1 positive cells [32,63,70]. In another report, however, NKG2D positive NK cell proportions were similar between healthy individuals and CML patients before treatment initiation [66].…”

Section: General Alterations In the Nk Cell Compartmentmentioning

confidence: 99%

NK Cells in Myeloproliferative Neoplasms (MPN)

Naismith

Steichen

Sopper

et al. 2021

Cancers

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Myeloproliferative neoplasms (MPNs) comprise a heterogenous group of hematologic neoplasms which are divided into Philadelphia positive (Ph+), and Philadelphia negative (Ph−) or classical MPNs. A variety of immunological factors including inflammatory, as well as immunomodulatory processes, closely interact with the disease phenotypes in MPNs. NK cells are important innate immune effectors and substantially contribute to tumor control. Changes to the absolute and proportionate numbers of NK cell, as well as phenotypical and functional alterations are seen in MPNs. In addition to the disease itself, a variety of therapeutic options in MPNs may modify NK cell characteristics. Reports of suppressive effects of MPN treatment strategies on NK cell activity have led to intensive investigations into the respective compounds, to elucidate the possible negative effects of MPN therapy on control of the leukemic clones. We hereby review the available literature on NK cells in Ph+ and Ph− MPNs and summarize today’s knowledge on disease-related alterations in this cell compartment with particular focus on known therapy-associated changes. Furthermore, we critically evaluate conflicting data with possible implications for future projects. We also aim to highlight the relevance of full NK cell functionality for disease control in MPNs and the importance of considering specific changes related to therapy in order to avoid suppressive effects on immune surveillance.

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“…In CML, the BCR-ABL fusion protein downregulates the expression of NKG2D on NK cells, through the chronic exposure to increased levels of NKG2DL. However, treatment with the tyrosine kinase inhibitor imatinib restored the expression of NKG2D in these patients [39]. Similarly, the expression of some NKG2DL, such as ULBP1, correlates with prognosis and survival after chemotherapy treatment in AML [36].…”

Section: Evidence Of Immune Surveillance Of Hematological Cancers mentioning

confidence: 99%

NK Cells in the Treatment of Hematological Malignancies

González-Rodríguez

Villa-Álvarez

Sordo‐Bahamonde

et al. 2019

JCM

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Natural killer (NK) cells have the innate ability to kill cancer cells, however, tumor cells may acquire the capability of evading the immune response, thereby leading to malignancies. Restoring or potentiation of this natural antitumor activity of NK cells has become a relevant therapeutic approach in cancer and, particularly, in hematological cancers. The use of tumor-specific antibodies that promote antibody-dependent cell-mediated cytotoxicity (ADCC) through the ligation of CD16 receptor on NK cells has become standard for many hematologic malignancies. Hematopoietic stem cell transplantation is another key therapeutic strategy that harnesses the alloreactivity of NK cells against cancer cells. This strategy may be refined by adoptive transfer of NK cells that may be previously expanded, activated, or redirected (chimeric antigen receptor (CAR)-NK cells) against cancer cells. The antitumor activity of NK cells can also be boosted by cytokines or immunostimulatory drugs such as lenalidomide or pomalidomide. Finally, targeting immunosubversive mechanisms developed by hematological cancers and, in particular, using antibodies that block NK cell inhibitory receptors and checkpoint proteins are novel promising therapeutic approaches in these malignant diseases.

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The role of natural killer cells in chronic myeloid leukemia

Cited by 9 publications

References 42 publications

Identification of Immunological Parameters as Predictive Biomarkers of Relapse in Patients with Chronic Myeloid Leukemia on Treatment-Free Remission

Identification of Immunological Parameters as Predictive Biomarkers of Relapse in Patients with Chronic Myeloid Leukemia on Treatment-Free Remission

NK Cells in Myeloproliferative Neoplasms (MPN)

NK Cells in the Treatment of Hematological Malignancies

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