Comprehensive Phenotyping of Human PB NK Cells by Flow Cytometry

Zotto, Genny Del; Antonini, Francesca; Pesce, Silvia; Moretta, Francesca; Moretta, Lorenzo; Marcenaro, Emanuela

doi:10.1002/cyto.a.24001

Cited by 30 publications

(31 citation statements)

References 94 publications

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“…NK-92 cells deliver a homogeneous cell inhabitant and can be simply cultivated under reliable manufacturing practice standards for wider clinical use, allowing the “off-the-shelf” construction of CAR-NK-92 cells ( 2 ). Stimulated PB-NK cells present a broader series of activating receptors and can be infused without irradiation, permitting them to grow in vivo ( 79 ). NK cells derived from pluripotent stem cells, iPSCs and hESCs, merge the clinical benefits of PB-NK and NK-92 cells because they show a phenotype similar to PB-NK cells and are a homogeneous inhabitant.…”

Section: Car-nk Cells Superiority Over Car-t Cellsmentioning

confidence: 99%

RETRACTED: CAR-NK Cell: A New Paradigm in Tumor Immunotherapy

et al. 2021

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The tumor microenvironment (TME) is greatly multifaceted and immune escape is an imperative attribute of tumors fostering tumor progression and metastasis. Based on reports, the restricted achievement attained by T cell immunotherapy reflects the prominence of emerging other innovative immunotherapeutics, in particular, natural killer (NK) cells-based treatments. Human NK cells act as the foremost innate immune effector cells against tumors and are vastly heterogeneous in the TME. Currently, there exists a rapidly evolving interest in the progress of chimeric antigen receptor (CAR)-engineered NK cells for tumor immunotherapy. CAR-NK cells superiorities over CAR-T cells in terms of better safety (e.g., absence or minimal cytokine release syndrome (CRS) and graft-versus-host disease (GVHD), engaging various mechanisms for stimulating cytotoxic function, and high feasibility for ‘off-the-shelf’ manufacturing. These effector cells could be modified to target various antigens, improve proliferation and persistence in vivo, upturn infiltration into tumors, and defeat resistant TME, which in turn, result in a desired anti-tumor response. More importantly, CAR-NK cells represent antigen receptors against tumor-associated antigens (TAAs), thereby redirecting the effector NK cells and supporting tumor-related immunosurveillance. In the current review, we focus on recent progress in the therapeutic competence of CAR-NK cells in solid tumors and offer a concise summary of the present hurdles affecting therapeutic outcomes of CAR-NK cell-based tumor immunotherapies.

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Section: Car-nk Cells Superiority Over Car-t Cellsmentioning

confidence: 99%

RETRACTED: CAR-NK Cell: A New Paradigm in Tumor Immunotherapy

et al. 2021

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“…NK cells can be subdivided into various subsets based on the relative expression of CD16 and CD56. The two classical NK cell subsets in peripheral blood are CD56 dim CD16 bright and CD56 bright CD16 −/dim NK cells [27]. Traditionally, the first population is predominant in peripheral blood and is considered to be the most cytotoxic subset, whereas the second are cytokine producers, and are primarily found in secondary lymphoid tissue and other tissues [28].…”

Section: Introductionmentioning

confidence: 99%

Immune checkpoint expression on peripheral cytotoxic lymphocytes in cervical cancer patients: moving beyond the PD-1/PD-L1 axis

Solorzano‐Ibarra

Alejandre-Gonzalez

Ortiz‐Lazareno

et al. 2021

Clinical and Experimental Immunology

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Summary Immune checkpoint therapy to reverse natural killer (NK) and T cell exhaustion has emerged as a promising treatment in various cancers. While anti‐programmed cell death 1 (PD‐1) pembrolizumab has recently gained Food and Drug Administration (FDA) approval for use in recurrent or metastatic cervical cancer, other checkpoint molecules, such as T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine‐based inhibition motif (ITIM) domains (TIGIT) and T cell immunoglobulin and mucin‐domain containing‐3 (Tim‐3), have yet to be fully explored in this disease. We report expression of TIGIT, Tim‐3 and PD‐1 on subsets of peripheral blood NK (CD56dim/negCD16bright/dim/neg and CD56brightCD16dim/neg) and T cells. The percentages of these cells were increased in women with cervical cancer and pre‐malignant lesions. PD‐1+ NK and T cells were likely to co‐express TIGIT and/or Tim‐3. These cells, with an apparently ‘exhausted’ phenotype, were augmented in patients. A subset of cells were also natural killer group 2 member D (NKG2D)‐ and DNAX accessory molecule 1 (DNAM‐1)‐positive. PD‐1int and PD‐1high T cells were notably increased in cervical cancer. Soluble programmed cell death ligand 1 (PD‐L1) was higher in cancer patient blood versus healthy donors and we observed a positive correlation between sPD‐L1 and PD‐1+ T cells in women with low‐grade lesions. Within the cancer group, there were no significant correlations between sPD‐L1 levels and cervical cancer stage. However, when comparing cancer versus healthy donors, we observed an inverse association between sPD‐L1 and total T cells and a correlation between sPD‐L1 and CD56dim NK cells. Our results may show an overview of the immune response towards pre‐cancerous lesions and cervical cancer, perhaps giving an early clue as to whom to administer blocking therapies. The increase of multiple checkpoint markers may aid in identifying patients uniquely responsive to combined antibody therapies.

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“…In physiological conditions, human NK cells include different cell subsets corresponding to different stages of NK cell differentiation (26). CD56bright CD16neg/dim NK cells (the major subset of NK cells in secondary lymphoid tissues) are considered as precursors of CD56dim CD16bright NK cells and have been usually considered "regulatory NK cells".…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, we studied the expression of NKG2C on all NK cells to evaluate their "adaptive" phenotype. NK cell subpopulations were analyzed based on a gate strategy already described in detail elsewhere by our group (26). To perform NK cell subpopulation analysis, PBMCs were acquired on a BD Fortessa X20 cytometer and analyzed using a Kaluza software (v.2.1, Beckman Coulter).…”

Section: Lymphocyte Subpopulations Analysismentioning

confidence: 99%

Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Refractory Hodgkin Lymphoma: A Feasible and Promising Salvage Therapy Associated With Expansion and Maturation of NK Cells

et al. 2021

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Immune checkpoint inhibitors (CI) have demonstrated clinical activity in Hodgkin Lymphoma (HL) patients relapsing after autologous stem cell transplantation (ASCT), although only 20% complete response (CR) rate was observed. The efficacy of CI is strictly related to the host immune competence, which is impaired in heavily pre-treated HL patients. Here, we aimed to enhance the activity of early post-ASCT CI (nivolumab) administration with the infusion of autologous lymphocytes (ALI). Twelve patients with relapse/refractory (R/R) HL (median age 28.5 years; range 18-65), underwent lymphocyte apheresis after first line chemotherapy and then proceeded to salvage therapy. Subsequently, 9 patients with progressive disease at ASCT received early post-transplant CI supported with four ALI, whereas 3 responding patients received ALI alone, as a control cohort. No severe adverse events were recorded. HL-treated patients achieved negative PET scan CR and 8 are alive and disease-free after a median follow-up of 28 months. Four patients underwent subsequent allogeneic SCT. Phenotypic analysis of circulating cells showed a faster expansion of highly differentiated NK cells in ALI plus nivolumab-treated patients as compared to control patients. Our data show anti-tumor activity with good tolerability of ALI + CI for R/R HL and suggest that this setting may accelerate NK cell development/maturation and favor the expansion of the “adaptive” NK cell compartment in patients with HCMV seropositivity, in the absence of HCMV reactivation.

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Comprehensive Phenotyping of Human PB NK Cells by Flow Cytometry

Cited by 30 publications

References 94 publications

RETRACTED: CAR-NK Cell: A New Paradigm in Tumor Immunotherapy

RETRACTED: CAR-NK Cell: A New Paradigm in Tumor Immunotherapy

Immune checkpoint expression on peripheral cytotoxic lymphocytes in cervical cancer patients: moving beyond the PD-1/PD-L1 axis

Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Refractory Hodgkin Lymphoma: A Feasible and Promising Salvage Therapy Associated With Expansion and Maturation of NK Cells

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