CD33 expression on natural killer cells is a potential confounder for residual disease detection in acute myeloid leukemia by flow cytometry

Eckel, Ashley M; Cherian, Sindhu; Miller, Valerie; Soma, Lorinda

doi:10.1002/cyto.b.21846

Cited by 15 publications

(15 citation statements)

References 16 publications

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“…CD33 is expressed on a heterogenous population of myeloid cells, and it does not distinguish MDSCs from TAMs or tumor-associated neutrophils (TANs) [ 20 ]. In addition, CD33 can be expressed on NK cells, but at lower levels compared to myeloid cell lineage [ 21 , 22 ]. CD33 high populations predominantly comprise monocytic populations and include cells with potentially high suppressive characteristics as identified by several groups [ 23 ].…”

Section: Resultsmentioning

confidence: 99%

Differential gene expression of tumor-infiltrating CD33+ myeloid cells in advanced- versus early-stage colorectal cancer

Toor

Taha

Nair

et al. 2020

Cancer Immunol Immunother

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Colorectal cancer (CRC) has high mortality rates, especially in patients with advanced disease stages, who often do not respond to therapy. The cellular components of the tumor microenvironment are essentially responsible for dictating disease progression and response to therapy. Expansion of different myeloid cell subsets in CRC tumors has been reported previously. However, tumor-infiltrating myeloid cells have both pro- and anti-tumor roles in disease progression. In this study, we performed transcriptomic profiling of cells of myeloid lineage (CD33+) from bulk CRC tumors at varying disease stages. We identified differentially expressed genes and pathways between CRC patients with advanced stage and early stages. We found that pro-angiogenic and hypoxia-related genes were upregulated, while genes related to immune and inflammatory responses were downregulated in CD33+ myeloid cells from patients with advanced stages, implying that immune cell recruitment and activation could be compromised in advanced disease stages. Moreover, we identified a unique “poor prognosis CD33+ gene signature” by aligning top upregulated and downregulated genes in tumor-infiltrating myeloid cells from our analyses with data from The Cancer Genome Atlas. Our results showed that this gene signature is an independent prognostic indicator for disease-specific survival in CRC patients, potentially reflecting its clinical importance.

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Section: Resultsmentioning

confidence: 99%

Differential gene expression of tumor-infiltrating CD33+ myeloid cells in advanced- versus early-stage colorectal cancer

Toor

Taha

Nair

et al. 2020

Cancer Immunol Immunother

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“…CD33 expression has been documented in subsets of activated NK cells (acting as an inhibitory receptor) but sufficient to impair NK viability using a tri-specific immune-ligand molecule [ 152 , 153 ]. NK cell CD33 knockout could thus serve a dual purpose of reducing fratricide and enhancing NK cell activation in a CD33 CAR-NK design.…”

Section: Car-nk: a Compelling Platform For Aml Immunotherapy?mentioning

confidence: 99%

Realizing Innate Potential: CAR-NK Cell Therapies for Acute Myeloid Leukemia

Gurney

O’Dwyer

2021

Cancers

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Next-generation cellular immunotherapies seek to improve the safety and efficacy of approved CD19 chimeric antigen receptor (CAR) T-cell products or apply their principles across a growing list of targets and diseases. Supported by promising early clinical experiences, CAR modified natural killer (CAR-NK) cell therapies represent a complementary and potentially off-the-shelf, allogeneic solution. While acute myeloid leukemia (AML) represents an intuitive disease in which to investigate CAR based immunotherapies, key biological differences to B-cell malignancies have complicated progress to date. As CAR-T cell trials treating AML are growing in number, several CAR-NK cell approaches are also in development. In this review we explore why CAR-NK cell therapies may be particularly suited to the treatment of AML. First, we examine the established role NK cells play in AML biology and the existing anti-leukemic activity of NK cell adoptive transfer. Next, we appraise potential AML target antigens and consider common and unique challenges posed relative to treating B-cell malignancies. We summarize the current landscape of CAR-NK development in AML, and potential targets to augment CAR-NK cell therapies pharmacologically and through genetic engineering. Finally, we consider the broader landscape of competing immunotherapeutic approaches to AML treatment. In doing so we evaluate the innate potential, status and remaining barriers for CAR-NK based AML immunotherapy.

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“…Unfortunately, the pool of available targets for a CAR remains limited in AML and can lead to NK cells fratricide. CD33 expression was stated in one subset of activated NK cells [ 151 , 152 ]. Several reports assessed the in-vitro function of CD123 CAR in NK cells, but failed to show a robust response in mouse models [ 149 , 153 , 154 , 155 ].…”

Section: Adoptive Cell Transfermentioning

confidence: 99%

Acute Myeloid Leukemia: Is It T Time?

Khoud

Ingegnere

Quesnel

et al. 2021

Cancers

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Acute myeloid leukemia (AML) is a heterogeneous disease driven by impaired differentiation of hematopoietic primitive cells toward myeloid lineages (monocytes, granulocytes, red blood cells, platelets), leading to expansion and accumulation of “stem” and/or “progenitor”-like or differentiated leukemic cells in the bone marrow and blood. AML progression alters the bone marrow microenvironment and inhibits hematopoiesis’ proper functioning, causing sustained cytopenia and immunodeficiency. This review describes how the AML microenvironment influences lymphoid lineages, particularly T lymphocytes that originate from the thymus and orchestrate adaptive immune response. We focus on the elderly population, which is mainly affected by this pathology. We discuss how a permissive AML microenvironment can alter and even worsen the thymic function, T cells’ peripheral homeostasis, phenotype, and functions. Based on the recent findings on the mechanisms supporting that AML induces quantitative and qualitative changes in T cells, we suggest and summarize current immunotherapeutic strategies and challenges to overcome these anomalies to improve the anti-leukemic immune response and the clinical outcome of patients.

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CD33 expression on natural killer cells is a potential confounder for residual disease detection in acute myeloid leukemia by flow cytometry

Cited by 15 publications

References 16 publications

Differential gene expression of tumor-infiltrating CD33+ myeloid cells in advanced- versus early-stage colorectal cancer

Differential gene expression of tumor-infiltrating CD33+ myeloid cells in advanced- versus early-stage colorectal cancer

Realizing Innate Potential: CAR-NK Cell Therapies for Acute Myeloid Leukemia

Acute Myeloid Leukemia: Is It T Time?

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