NK cells from malignant pleural effusions are not anergic but produce cytokines and display strong antitumor activity on short‐term IL‐2 activation

Vacca, Paola; Martini, Stefania; Garelli, Valentina; Passalacqua, Giovanni; Moretta, Alessandro; Mingari, Maria Cristina

doi:10.1002/eji.201242783

Cited by 41 publications

(44 citation statements)

References 47 publications

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“…We have recently shown that NK cells isolated from malignant pleural effusions (PE-NK cells) are not anergic and, upon IL-2 activation, they could efficiently kill autologous tumor cells [82]. In addition, they rapidly release cytokines (IFN-γ and TNF) and undergo degranulation upon exposure to tumor cells.…”

Section: Nk Cell Therapy Of Tumorsmentioning

confidence: 99%

Human natural killer cells: news in the therapy of solid tumors and high-risk leukemias

Pietra

Vitale

Pende

et al. 2015

Cancer Immunol Immunother

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It is well established that natural killer (NK) cells play an important role in the immunity against cancer, while the involvement of other recently identified, NK-related innate lymphoid cells is still poorly defined. In the haploidentical hematopoietic stem cell transplantation for the therapy of high-risk leukemias, NK cells have been shown to exert a key role in killing leukemic blasts residual after conditioning. While the clinical results in the cure of leukemias are excellent, the exploitation of NK cells in the therapy of solid tumors is still limited and unsatisfactory. In solid tumors, NK cell function may be inhibited via different mechanisms, occurring primarily at the tumor site. The cellular interactions in the tumor microenvironment involve tumor cells, stromal cells and resident or recruited leukocytes and may favor tumor evasion from the host's defenses. In this context, a number of cytokines, growth factors and enzymes synthesized by tumor cells, stromal cells, suppressive/regulatory myeloid and lymphoid cells may substantially impair the function of different tumor-reactive effector cells, including NK cells. The identification and characterization of such mechanisms may offer clues for the development of new immunotherapeutic strategies to restore effective anti-tumor responses. In order to harness NK cell-based immunotherapies, several approaches have been proposed, including reinforcement of NK cell cytotoxicity by means of specific cytokines, antibodies or drugs. These new tools may improve NK cell function and/or increase tumor susceptibility to NK-mediated killing. Hence, the integration of NK-based immunotherapies with conventional anti-tumor therapies may increase chances of successful cancer treatment.

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Section: Nk Cell Therapy Of Tumorsmentioning

confidence: 99%

Human natural killer cells: news in the therapy of solid tumors and high-risk leukemias

Pietra

Vitale

Pende

et al. 2015

Cancer Immunol Immunother

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“…Interestingly, recent experiments in which NK cells were isolated from neoplastic pleural effusions showed that they were not anergic, but rather displayed a strong cytolytic activity upon short-term culture with IL-2 or IL-15. This finding may have relevant implications for NK cell-based adoptive immunotherapy in patients with tumors localized to the pleural cavity [104]. …”

Section: Nk Cell Interactions With Solid Tumorsmentioning

confidence: 99%

Human Natural Killer Cells: Origin, Receptors, Function, and Clinical Applications

Moretta

Montaldo

Vacca

et al. 2014

Int Arch Allergy Immunol

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117

101

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Natural killer (NK) cells are important effectors playing a relevant role in innate immunity, primarily in tumor surveillance and in defenses against viruses. Human NK cells recognize HLA class I molecules through surface receptors (KIR and NKG2A) that inhibit NK cell function and kill target cells that have lost (or underexpress) HLA class I molecules as it occurs in tumors or virus-infected cells. NK cell activation is mediated by an array of activating receptors and co-receptors that recognize ligands expressed primarily on tumors or virus-infected cells. In vivo anti-tumor NK cell activity may be suppressed by tumor or tumor-associated cells. Alloreactive NK cells (i.e. those that are not inhibited by the HLA class I alleles of the patient) derived from HSC of haploidentical donors play a major role in the cure of high-risk leukemia, by killing leukemia blasts and patient's DC, thus preventing tumor relapses and graft-versus-host disease. The expression of the HLA-C2-specific activating KIR2DS1 may also contribute to NK alloreactivity in patients expressing C2 alleles. A clear correlation has been proven between the size of the alloreactive NK cell population and the clinical outcome. Recently, haplo-HSCT has been further improved with the direct infusion, together with HSC, of donor-derived, mature alloreactive NK cells and TCRγδ⁺ T cells - both contributing to a prompt anti-leukemia effect together with an efficient defense against pathogens during the 6- to 8-week interval required for the generation of alloreactive NK cells from HSC.

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“…27,28 Purified NK cells were cultured on allogeneic irradiated feeder cells in the presence of interleukin-2 (100 U/mL) and phytohemagglutinin (1.5 ng/mL, Gibco, Life Technologies).…”

mentioning

confidence: 99%

HLA-G is a component of the chronic lymphocytic leukemia escape repertoire to generate immune suppression: impact of the HLA-G 14 base pair (rs66554220) polymorphism

et al. 2013

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NK cells from malignant pleural effusions are not anergic but produce cytokines and display strong antitumor activity on short‐term IL‐2 activation

Cited by 41 publications

References 47 publications

Human natural killer cells: news in the therapy of solid tumors and high-risk leukemias

Human natural killer cells: news in the therapy of solid tumors and high-risk leukemias

Human Natural Killer Cells: Origin, Receptors, Function, and Clinical Applications

HLA-G is a component of the chronic lymphocytic leukemia escape repertoire to generate immune suppression: impact of the HLA-G 14 base pair (rs66554220) polymorphism

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