The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk

Gabrielli, Sara; Ortolani, Claudio; Zotto, Genny Del; Luchetti, Francesca; Canonico, Barbara; Buccella, Flavia; Artico, Marco; Papa, Stefano; Zamai, Loris

doi:10.1155/2016/1376595

Cited by 31 publications

(28 citation statements)

References 109 publications

(155 reference statements)

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“…To this regard, the restricted expression of CD48 to hematopoietic cells, sets limits to 2B4-dependent synergistic cytotoxic activity of CD56 dim NK cells suggesting that CD56 dim NK cells may represent a cytotoxic effector subset deeply involved in patrolling hematopoietic compartment. Indeed, allogeneic hematopoietic stem cell transplantation (HSCT) from selected donors showed to generate alloreactive CD56 dim NK cells able to kill not only patient's neoplastic cells, but also his dendritic cells (DCs) and T lymphocytes, reducing leukemic relapse, thus graft versus host disease (GvHD), and graft rejection [1][2][3][4]. The observation that CD48-hematopoietic antigen can synergistically triggers CD56 dim NK cell cytotoxicity possibly provides a further rational for the lack of NK mediated graft versus host disease (GvHD) in KIR ligand-mismatched haploidentical hematopoietic transplantation.…”

Section: B4 Preferentially Drives Nk Cell Function Against Hematopoiementioning

confidence: 99%

“…Natural killer (NK) cells are large granular cytotoxic lymphocytes considered part of the innate immune system. They provide rapid responses against virally infected and tumour cells; for these features, NK cells have been successfully employed in several immunotherapeutic strategies [1][2][3][4][5][6]. NK cells express both activating and inhibitory receptors and the balance between their signalling plays an important role in self-tolerance and in NK cell activity [2,7,8].…”

Section: Introductionmentioning

confidence: 99%

“…Several receptors have been described to participate in the spontaneous NK cell activation, among them NKp46 (CD335), NKp30 (CD337) and NKp44 (CD336), collectively termed Natural Cytotoxicity Receptors (NCRs), NKG2D (CD314), DNAM-1 (CD226), 2B4 (CD244), LFA-1 (CD11a-CD18) and CD2 are some of the most important [7,8,[26][27][28][29]. Activating receptors can recognize either self-ligands, whose expression is usually upregulated upon cellular stress, or exogenous microbial molecules and associate with different intracytoplasmic molecules [2,3,7,30,31].…”

Section: Introductionmentioning

confidence: 99%

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Understanding the Synergy of NKp46 and Co-Activating Signals in Various NK Cell Subpopulations: Paving the Way for More Successful NK-Cell-Based Immunotherapy

Zamai

Zotto

Buccella

et al. 2020

Cells

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The NK cell population is characterized by distinct NK cell subsets that respond differently to the various activating stimuli. For this reason, the determination of the optimal cytotoxic activation of the different NK cell subsets can be a crucial aspect to be exploited to counter cancer cells in oncologic patients. To evaluate how the triggering of different combination of activating receptors can affect the cytotoxic responses of different NK cell subsets, we developed a microbead-based degranulation assay. By using this new assay, we were able to detect CD107a+ degranulating NK cells even within the less cytotoxic subsets (i.e., resting CD56bright and unlicensed CD56dim NK cells), thus demonstrating its high sensitivity. Interestingly, signals delivered by the co-engagement of NKp46 with 2B4, but not with CD2 or DNAM-1, strongly cooperate to enhance degranulation on both licensed and unlicensed CD56dim NK cells. Of note, 2B4 is known to bind CD48 hematopoietic antigen, therefore this observation may provide the rationale why CD56dim subset expansion correlates with successful hematopoietic stem cell transplantation mediated by alloreactive NK cells against host T, DC and leukemic cells, while sparing host non-hematopoietic tissues and graft versus host disease. The assay further confirms that activation of LFA-1 on NK cells leads to their granule polarization, even if, in some cases, this also takes to an inhibition of NK cell degranulation, suggesting that LFA-1 engagement by ICAMs on target cells may differently affect NK cell response. Finally, we observed that NK cells undergo a time-dependent spontaneous (cytokine-independent) activation after blood withdrawal, an aspect that may strongly bias the evaluation of the resting NK cell response. Altogether our data may pave the way to develop new NK cell activation and expansion strategies that target the highly cytotoxic CD56dim NK cells and can be feasible and useful for cancer and viral infection treatment.

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Section: B4 Preferentially Drives Nk Cell Function Against Hematopoiementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Understanding the Synergy of NKp46 and Co-Activating Signals in Various NK Cell Subpopulations: Paving the Way for More Successful NK-Cell-Based Immunotherapy

Zamai

Zotto

Buccella

et al. 2020

Cells

Self Cite

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“…Recent data demonstrating vaccine-mediated NK-cell activation suggest potential synergy with adoptive immunotherapy with NK cells. 83…”

Section: Vaccine For Hematological Malignancymentioning

confidence: 99%

Vaccine therapy in hematologic malignancies

Avigan

Rosenblatt

2018

Blood

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Immune-based therapy has emerged as a paradigm shift in cancer therapy with dramatic responses observed in previously incurable disease. Cancer vaccines are being developed to disrupt tumor-associated tolerance and activate and selectively expand tumor-specific lymphocytes within the native effector cell repertoire while maintaining immune-regulatory protection against autoimmunity. Although individual antigen approaches result in immune response with a suggestion of clinical effect in some settings, broader efficacy may be dependent on presentation of multiple antigens that capture clonal diversity presented in the context of functionally potent antigen-presenting cells. The use of whole cell-based strategies such as dendritic cell/tumor fusions have yielded provocative results in single-arm studies and are currently being explored in multicenter randomized trials. The posttransplant setting is a potentially promising platform for vaccination due to cytoreduction and relative depletion of inhibitory accessory cells fostering greater immune responsiveness. Integration of these efforts with other immunotherapeutic strategies and agents that target the tumor microenvironment is being studied in an effort to generate durable immunologic responses with clinically meaningful impact on disease.

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“…Оказалось, что различие между определени-ем с помощью тест-системы CD3/CD16/CD56 и с помощью CD3/CD16 является статистически значимым (p < 0,05). Было показано, что основ- , на долю кото-рых приходится до 10% [13,20,25,27].…”

Section: результатыunclassified

Heterogeneity of Nk and NKT Lymphocyte Populations in Healthy Donors

Tabakov¹,

Заботина²,

Борунова³

et al. 2017

Med. immunol.

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Резюме. Натуральные киллеры (NK) и NKT-лимфоциты являются важными составляющими врожденного иммунитета и играют роль первой линии защиты от онкологических заболеваний. Данные популяции отличаются высокой гетерогенностью и разделяются на несколько субпопуля-ций, отличающихся по степени экспрессии маркеров CD56 и CD16 и функциональной активно-стью. Исследование гетерогенности данных популяций лимфоцитов у здоровых доноров актуаль-но, так как является основой для изучения нарушений баланса между различными субпопуляциями у онкологических больных. Изменения соотношения выше представленных субпопуляций могут обладать прогностическим и клиническим значением при опухолевых заболеваниях. Было проведе-но исследование лимфоцитов периферической крови 50 здоровых доноров. При анализе популяции NK-лимфоцитов было выявлено 18,0±11,3% антиген-положительных клеток, колебания значений составило от 7,6 до 29,2%, в то время как количество клеток с фенотипами CD3 dim CD16 dim , не содержащая внутриклеточный перфорин (2,0%). Популяция NKT-клеток с фенотипом СD3 + CD16/СD56 + вы-является в 7,1% (25% -3,45; 75% -8,75) антиген-положительных клеток в диапазоне от 2,5 до 11,9% и не подчиняется законам нормального распределения. При анализе с помощью комбинации МКА CD3/CD56/CD16 количество CD3 + CD56 + клеток составило 4,33% (25% -2,25; 75% -7,3), а коли-чество CD3 + CD16 + -3,087% (25% -0,9; 75% -6,2). Оказалось, что различия между определением с помощью тест-системы CD3/CD16/CD56 и с помощью CD3/CD16 является статистически значи- Россия, Москва, Каширское шоссе, 23. Тел.: 8 (962) 956-25-97.

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The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk

Cited by 31 publications

References 109 publications

Understanding the Synergy of NKp46 and Co-Activating Signals in Various NK Cell Subpopulations: Paving the Way for More Successful NK-Cell-Based Immunotherapy

Understanding the Synergy of NKp46 and Co-Activating Signals in Various NK Cell Subpopulations: Paving the Way for More Successful NK-Cell-Based Immunotherapy

Vaccine therapy in hematologic malignancies

Heterogeneity of Nk and NKT Lymphocyte Populations in Healthy Donors

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