NK cells from pleural effusions are potent antitumor effector cells

Terme, Magali; Fridman, Wolf‐Herman; Tartour, Éric

doi:10.1002/eji.201243264

Cited by 15 publications

(11 citation statements)

References 32 publications

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“…In addition, they rapidly release cytokines (IFN-γ and TNF) and undergo degranulation upon exposure to tumor cells. These data suggest the possibility of treating primary or metastatic pleural tumors with local infusion of IL-2 and/or autologous IL-2-activated PE-NK cells [83,84]. However, clinical trials using high doses of IL-2 for advanced melanoma and renal carcinoma showed limited clinical benefits.…”

Section: Nk Cell Therapy Of Tumorsmentioning

confidence: 87%

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: 87%

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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“…Natural killer (NK) cells exert an antibody-independent cytotoxic effect against cancer cells through NK receptors, including NKG2D, and killer inhibitory receptors (KIR; refs. [25][26][27][28]. NKG2D is a receptor for different activating ligands overexpressed on cancer cells, whereas KIRs recognize MHC class I molecules; NK cells are also activated by the decrease in MHC class I molecules reported on cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Prospective Evaluation of Cetuximab-Mediated Antibody-Dependent Cell Cytotoxicity in Metastatic Colorectal Cancer Patients Predicts Treatment Efficacy

Trotta¹,

Ottaiano

Romano

et al. 2016

Cancer Immunology Research

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Cetuximab is a monoclonal antibody to the EGFR that induces antibody-dependent cell cytotoxicity (ADCC) through Fcg receptors on immune cells. Although SNPs in genes encoding Fcg receptors are functionally relevant to cetuximab-mediated ADCC in colorectal cancer, a direct correlation between in vitro ADCC and clinical response to cetuximab is not defined. We therefore enrolled 96 consecutive metastatic colorectal cancer (mCRC) patients at diagnosis in a study that assessed FcgR status and cetuximab-mediated ADCC. Patients carrying the FcgRIIa H alleles 131H/H and 131H/R had significantly higher ADCC compared with patients with the 131R/R alleles (P ¼ 0.013). Patients carrying FcgRIIIa genotypes with the V alleles 158V/V and 158V/F displayed higher ADCC compared with patients carrying the 158F/F genotype (P ¼ 0.001). Progression-free survival of patients with an FcgRIIIa 158V allele was significantly longer compared with patients carrying 158F/F (P ¼ 0.05), whereas no significant difference was observed for overall survival. Twentyeight of 50 mCRC patients with wild-type KRAS received cetuximab. The average ADCC-mediated killing was 30% of assay targets for patients who experienced cetuximab complete or partial response, 21% in patients with stable disease and 9% in patients with progressive disease. To characterize basal natural killer (NK) activity, cytotoxicity was evaluated in 39 of 96 mCRC patients. Patients who responded to first-line treatment had higher NK-cell cytotoxicity. Thus, although limited to this cohort of patients, in vitro cetuximab-mediated ADCC correlated with FcgR polymorphisms and predicted cetuximab responsiveness.

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“…Thus, primary strategies in immunotherapy are aimed to boost in vivo NK cell-mediated antitumor activity. One approach is based on the in vivo administration of cytokines, such as IL-2 and IL-15, that determine NK cell activation, differentiation, and expansion (8,(28)(29)(30)(31)(32). IL-2 administration was approved in the 1990s for the treatment of metastatic RCC 2.…”

Section: Boosting In Vivo Nk Cells With Immune Stimulatory Cytokinesmentioning

confidence: 99%

Exploiting Human NK Cells in Tumor Therapy

et al. 2020

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NK cells play an important role in the innate defenses against tumor growth and metastases. Human NK cell activation and function are regulated by an array of HLA class I-specific inhibitory receptors and activating receptors recognizing ligands expressed de novo on tumor or virus-infected cells. NK cells have been exploited in immunotherapy of cancer, including: (1) the in vivo infusion of IL-2 or IL-15, cytokines inducing activation and proliferation of NK cells that are frequently impaired in cancer patients. Nonetheless, the significant toxicity experienced, primarily with IL-2, limited their use except for combination therapies, e.g., IL-15 with checkpoint inhibitors; (2) the adoptive immunotherapy with cytokine-induced NK cells had effect on some melanoma metastases (lung), while other localizations were not affected; (3) a remarkable evolution of adoptive cell therapy is represented by NK cells engineered with CAR-targeting tumor antigens (CAR-NK). CAR-NK cells complement CART cells as they do not cause GvHD and may be obtained from unrelated donors. Accordingly, CAR-NK cells may represent an "off-the-shelf" tool, readily available for effective tumor therapy; (4) the efficacy of adoptive cell therapy in cancer is also witnessed by the αβT cell-and B cell-depleted haploidentical HSC transplantation in which the infusion of donor NK cells and γδT cells, together with HSC, sharply reduces leukemia relapses and infections; (5) a true revolution in tumor therapy is the use of mAbs targeting checkpoint inhibitors including PD-1, CTLA-4, the HLA class I-specific KIR, and NKG2A. Since PD-1 is expressed not only by tumor-associated T cells but also by NK cells, its blocking might unleash NK cells playing a crucial effector role against HLA class I-deficient tumors that are undetectable by T cells.

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NK cells from pleural effusions are potent antitumor effector cells

Cited by 15 publications

References 32 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

Prospective Evaluation of Cetuximab-Mediated Antibody-Dependent Cell Cytotoxicity in Metastatic Colorectal Cancer Patients Predicts Treatment Efficacy

Exploiting Human NK Cells in Tumor Therapy

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