Increased natural killer cell expression of CD16, augmented binding and ADCC activity to rituximab among individuals expressing the FcγRIIIa-158 V/V and V/F polymorphism

Hatjiharissi, Evdoxia; Liu, Xu; Santos, Daniel Ditzel; Hunter, Zachary; Ciccarelli, Bryan; Verselis, Sigitas; Modica, Michael; Cao, Yang; Manning, R.J.; Leleu, Xavier; Dimmock, Elizabeth A.; Kortsaris, Alexandros; Mitsiades, Constantine S.; Anderson, Kenneth C.; Fox, Edward A.; Treon, Steven P.

doi:10.1182/blood-2007-01-070656

Cited by 238 publications

(200 citation statements)

References 16 publications

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“…4 The importance of ADCC in rituximab efficacy is supported by 4 non-Hodgkin lymphoma (NHL) trials in which patients bearing the Fc␥RIIA-H131R and Fc␥RIIIA-V158F highaffinity Fc␥R polymorphisms exhibited improved response to rituximab therapy. [5][6][7][8][9] Whereas in vitro studies demonstrate rituximab can mediate ADCC against primary CLL cells, 2,10 one preliminary study did not identify correlation of response with high-affinity Fc␥R polymorphisms. 11 This has prompted investigation of innate immune enhancing agents to improve both ADCC and rituximab efficacy.…”

Section: Introductionmentioning

confidence: 99%

Lenalidomide down-regulates the CD20 antigen and antagonizes direct and antibody-dependent cellular cytotoxicity of rituximab on primary chronic lymphocytic leukemia cells

Lapalombella¹,

Yu²,

Triantafillou³

et al. 2008

Blood

103

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Lenalidomide, an immunomodulatory agent that enhances antibody-dependent cellular cytotoxicity (ADCC), is currently being investigated as a therapy for chronic lymphocytic leukemia (CLL). The anti-CD20 antibody rituximab is active in CLL and represents a rational agent to combine with lenalidomide. We therefore examined whether lenalidomide combined with rituximab enhances direct apoptosis and ADCC in CLL cells. In contrast to previous reports using CD20-positive lymphoma cell lines, lenalidomide downregulated CD20 surface antigen expression in CLL patient cells via enhanced internalization, without influencing transcription. The CD20 surface antigen internalization enhanced delivery of an oligonucleotide incorporated into anti-CD20 immunoliposomes. In addition, CD20 surface antigen down-modulation by lenalidomide in CLL was accompanied by diminished rituximab-mediated apoptosis and ADCC. These observations suggest a need for alternative sequencing strategies to avoid antagonism between lenalidomide and rituximab therapy in CLL. In addition, they suggest that lenalidomide therapy might be useful to enhance targeted delivery of RNAi-based therapies using CD20 immunoliposomes in B-cell malignancies. (Blood. 2008;112: 5180-5189)

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Section: Introductionmentioning

confidence: 99%

Lenalidomide down-regulates the CD20 antigen and antagonizes direct and antibody-dependent cellular cytotoxicity of rituximab on primary chronic lymphocytic leukemia cells

Lapalombella¹,

Yu²,

Triantafillou³

et al. 2008

Blood

103

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“…Two groups separately demonstrated that HIV-infected subjects carrying a CD16 polymorphism, which increases the IgG binding of the receptor and enhances the NK cell ADCC potential (50), exhibit faster disease progression (51,52). It should be noted that an additional study by Forthal et al (53) did not observe an effect of CD16 polymorphisms on HIV disease progression.…”

Section: Discussionmentioning

confidence: 99%

Anti-HIV Antibody–Dependent Activation of NK Cells Impairs NKp46 Expression

Parsons

Tang

Jegaskanda

et al. 2014

The Journal of Immunology

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There is much interest in the potential of Ab-dependent cellular cytotoxicity (ADCC) to slow disease progression following HIV infection. Despite several studies demonstrating a positive association between ADCC and slower disease progression, it is possible that continued stimulation of NK cells by ADCC during chronic HIV infection could render these cells dysfunctional. Indeed, activation of NK cells by ADCC results in matrix metalloproteinase–induced reductions in CD16 expression and activation refractory periods. In addition, ex vivo analyses of NK cells from HIV-infected individuals revealed other alterations in phenotype, such as decreased expression of the activating NKp46 receptor that is essential for NK-mediated antitumor responses and immunity from infection. Because NKp46 shares a signaling pathway with CD16, we hypothesized that activation-induced downregulation of both receptors could be controlled by a common mechanism. We found that activation of NK cells by anti-HIV or anti-CD16 Abs resulted in NKp46 downregulation. The addition of a matrix metalloproteinase inhibitor attenuated NKp46 downregulation following NK cell activation by anti-HIV Abs. Consequently, these results suggest that continued stimulation through CD16 has the potential to impair natural cytotoxicity via attenuation of NKp46-dependent signals.

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“…Of note, NKG2C bright NK cell expansions, as well as their dominance in the Ab-dependent cytokine response, was observed in individuals with different CD16 (158V/F) genotypes regardless of their reported influence on Ab binding and Ab-mediated ADCC (52,53). Whether the frequency of NKG2C bright NK cells, not appreciated through genetic analysis, could explain the controversial data in studies addressing the impact of those polymorphisms in clinical contexts such as Ab-based anticancer therapies deserves attention (54).…”

Section: Differentiation Of Nkg2c Bright Nk Cells As Cytokine Producementioning

confidence: 94%

Antibody-Mediated Response of NKG2Cbright NK Cells against Human Cytomegalovirus

Costa‐García

Vera

Moraru³

et al. 2015

The Journal of Immunology

105

108

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Human CMV (HCMV) infection promotes a variable and persistent expansion of functionally mature NKG2Cbright NK cells. We analyzed NKG2Cbright NK cell responses triggered by Abs from HCMV+ sera against HCMV-infected MRC5 fibroblasts. Specific Abs promoted the degranulation (i.e., CD107a expression) and the production of cytokines (TNF-α and IFN-γ) by a significant fraction of NK cells, exceeding the low natural cytotoxicity against HCMV-infected targets. NK cell–mediated Ab-dependent cell-mediated cytotoxicity was limited by viral Ag availability and HLA class I expression on infected cells early postinfection and increased at late stages, overcoming viral immunoevasion strategies. Moreover, the presence of specific IgG triggered the activation of NK cells against Ab-opsonized cell-free HCMV virions. As compared with NKG2A+ NK cells, a significant proportion of NKG2Cbright NK cells was FcεR γ-chain defective and highly responsive to Ab-driven activation, being particularly efficient in the production of antiviral cytokines, mainly TNF-α. Remarkably, the expansion of NKG2Cbright NK cells in HCMV+ subjects was related to the overall magnitude of TNF-α and IFN-γ cytokine secretion upon Ab-dependent and -independent activation. We show the power and sensitivity of the anti-HCMV response resulting from the cooperation between specific Abs and the NKG2Cbright NK-cell subset. Furthermore, we disclose the proinflammatory potential of NKG2Cbright NK cells, a variable that could influence the individual responses to other pathogens and tumors.

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Increased natural killer cell expression of CD16, augmented binding and ADCC activity to rituximab among individuals expressing the FcγRIIIa-158 V/V and V/F polymorphism

Cited by 238 publications

References 16 publications

Lenalidomide down-regulates the CD20 antigen and antagonizes direct and antibody-dependent cellular cytotoxicity of rituximab on primary chronic lymphocytic leukemia cells

Lenalidomide down-regulates the CD20 antigen and antagonizes direct and antibody-dependent cellular cytotoxicity of rituximab on primary chronic lymphocytic leukemia cells

Anti-HIV Antibody–Dependent Activation of NK Cells Impairs NKp46 Expression

Antibody-Mediated Response of NKG2Cbright NK Cells against Human Cytomegalovirus

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