Dysregulated Activating and Inhibitory Receptors on Natural Killer Cells Predicts Immune Escape and Poor Outcomes in Acute Myeloid Leukemia

Costa, A. F O; Kuznetsova, Valeriya; Marani, L; Lopes, Izabela Aparecida; Binelli, Larissa Sarri; Scheucher, Priscila Santos; Schiavinato, Josiane Lilian dos Santos; Faria, Joana T B; Madeira, Maria Isabel Ayrosa; Pagnano, Katia B; Duarte, Bruno; Glória, Ana; Rego, Eduardo Magalhães; Traina, Fabı́ola; Welner, Robert S.; Figueiredo-Pontes, Lorena Lôbo de

doi:10.1182/blood-2022-168178

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“…Clinical studies observed a significant reduction in the number of NK cells in AML patients compared to normal values and the frequency of NK cells was inversely proportionate with prognosis and OS [ 90 , 91 ]. Furthermore, studies found that NK cells of AML patients have a significantly lower capacity to secrete IFNγ and showed numerous signs of an exhausted phenotype, as compared to healthy controls [ 92 , 93 ]. These include underexpression of activating receptors such as NKG2D, DNAM-1 and NKp30 as well as overexpression of inhibitory receptors such as NKG2A and KIR2DL1 [ 93 , 94 ].…”

Section: The Innate Immune System In the Tumor Microenvironment Of Amlmentioning

confidence: 99%

“…Furthermore, studies found that NK cells of AML patients have a significantly lower capacity to secrete IFNγ and showed numerous signs of an exhausted phenotype, as compared to healthy controls [ 92 , 93 ]. These include underexpression of activating receptors such as NKG2D, DNAM-1 and NKp30 as well as overexpression of inhibitory receptors such as NKG2A and KIR2DL1 [ 93 , 94 ].…”

Section: The Innate Immune System In the Tumor Microenvironment Of Amlmentioning

confidence: 99%

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Targeting the innate immune system in pediatric and adult AML

Perzolli,

Koedijk,

Zwaan

et al. 2024

Leukemia

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While the introduction of T cell-based immunotherapies has improved outcomes in many cancer types, the development of immunotherapies for both adult and pediatric AML has been relatively slow and limited. In addition to the need to identify suitable target antigens, a better understanding of the immunosuppressive tumor microenvironment is necessary for the design of novel immunotherapy approaches. To date, most immune characterization studies in AML have focused on T cells, while innate immune lineages such as monocytes, granulocytes and natural killer (NK) cells, received less attention. In solid cancers, studies have shown that innate immune cells, such as macrophages, myeloid-derived suppressor cells and neutrophils are highly plastic and may differentiate into immunosuppressive cells depending on signals received in their microenvironment, while NK cells appear to be functionally impaired. Hence, an in-depth characterization of the innate immune compartment in the TME is urgently needed to guide the development of immunotherapeutic interventions for AML. In this review, we summarize the current knowledge on the innate immune compartment in AML, and we discuss how targeting its components may enhance T cell-based- and other immunotherapeutic approaches.

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