TLR/NCR/KIR: Which One to Use and When?

Sivori, Simona; Carlomagno, Simona; Pesce, Silvia; Moretta, Alessandro; Vitale, Massimo; Marcenaro, Emanuela

doi:10.3389/fimmu.2014.00105

Cited by 68 publications

(65 citation statements)

References 117 publications

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“…human NK cells express TLR2, TLR3, TLR5, TLR7/8 and TLR9), epithelial and endothelial cells etc. express various TLRs, which help in the recognition of PAMPs in extracellular as well as intracellular environment [64][65][66][67][68][69][70][71][72]86,87]. Thus, TLR mediated recognition of pathogens by innate immune cells plays a very important role in the induction of pro-inflammatory immune response required to clear the infection.…”

Section: Current Scenario In Tlr Biology Regulation Of Innate Immunementioning

confidence: 99%

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Kumar

2018

International Immunopharmacology

461

288

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The immune system is a very diverse system of the host that evolved during evolution to cope with various pathogens present in the vicinity of environmental surroundings inhabited by multicellular organisms ranging from achordates to chordates (including humans). For example, cells of immune system express various pattern recognition receptors (PRRs) that detect danger via recognizing specific pathogen-associated molecular patterns (PAMPs) and mount a specific immune response. Toll-like receptors (TLRs) are one of these PRRs expressed by various immune cells. However, they were first discovered in the Drosophila melanogaster (common fruit fly) as genes/proteins important in embryonic development and dorso-ventral body patterning/polarity. Till date, 13 different types of TLRs (TLR1-TLR13) have been discovered and described in mammals since the first discovery of TLR4 in humans in late 1997. This discovery of TLR4 in humans revolutionized the field of innate immunity and thus the immunology and host-pathogen interaction. Since then TLRs are found to be expressed on various immune cells and have been targeted for therapeutic drug development for various infectious and inflammatory diseases including cancer. Even, Single nucleotide polymorphisms (SNPs) among various TLR genes have been identified among the different human population and their association with susceptibility/resistance to certain infections and other inflammatory diseases. Thus, in the present review the current and future importance of TLRs in immunity, their pattern of expression among various immune cells along with TLR based therapeutic approach is reviewed.

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Section: Current Scenario In Tlr Biology Regulation Of Innate Immunementioning

confidence: 99%

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Kumar

2018

International Immunopharmacology

461

288

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“…An additional immune‐therapeutic approach developed over the past recent years relies on the production of blocking mAbs against HLA‐I‐specific iNKRs. The rationale of this novel strategy is to increase NK cell alloreactivity, thus mimicking the “missing‐self” response and engaging the action of aNKRs including NKp46, NKp30 (the two main activating NK receptors), and NKG2D . In this regard, two IgG4 mAbs respectively blocking KIR2D/HLA‐C (IPH2102, lirilumab, Innate Pharma) and NKG2A/HLA‐E (IPH2201, monalizumab, Innate Pharma) have been recently developed for clinical application.…”

Section: Inhibition Of Nkg2a Checkpoint As Novel Immunotherapymentioning

confidence: 99%

Targeting NKG2A to elucidate natural killer cell ontogenesis and to develop novel immune-therapeutic strategies in cancer therapy

Zaghi

Calvi

Marcenaro

et al. 2019

Journal of Leukocyte Biology

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Natural Killer (NK) cells are innate immune cells with a primary role in the immune surveillance against non‐self‐cells. NK cell recognition of “self” relies on the surface expression on autologous cells of MHC class I (MHC‐I) molecules. Either the absence or the down‐modulation of MHC‐I on target cells “license” NK cells to kill threatening tumor‐transformed or virally infected cells. This phenomenon is controlled by a limited repertoire of activating and inhibitory NK receptors (aNKRs and iNKRs) that tunes NK cell activation and effector functions. Hence, the calibration of NK cell alloreactivity depends on the ability of iNKRs to bind MHC‐I complex and these interactions are key in regulating both NK cell differentiation and effector functions. Indeed, the presence of iNKRs specific for self‐MHC haplotypes (i) plays a role in the “licensing/education” process that controls the responsiveness of mature NK cells and prevents their activation against the “self” and (ii) is exploited by tumor cells to escape from NK cell cytotoxicity. Herein, we review our current knowledge on function and clinical application of NKG2A, a C‐type lectin iNKR that binds specific haplotypes of human leukocyte antigens early during the NK cell maturation process, thus contributing to modulate the terminal maturation of NK cells as potent effectors against cancers cells. These NKG2A‐mediated mechanisms are currently being exploited for developing promising immune‐therapeutic strategies to improve the prognosis of solid and blood tumors and to ameliorate the clinical outcome of patients undergone allogeneic hematopoietic stem cell transplantation to treat high‐risk hematologic malignancies.

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“…Thus, KIR3DL2 binds CpG molecules at the cell surface and shuttles them to early endosomes where TLR9 are located. TLR9 signaling by CpG activates NK cells and amplifies NK cell cytotoxicity and cytokine production [66,67]. …”

Section: Nk Cell Function Is Regulated By Activating and Inhibitory Rmentioning

confidence: 99%

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

Moretta

Montaldo

Vacca

et al. 2014

Int Arch Allergy Immunol

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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TLR/NCR/KIR: Which One to Use and When?

Cited by 68 publications

References 117 publications

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Targeting NKG2A to elucidate natural killer cell ontogenesis and to develop novel immune-therapeutic strategies in cancer therapy

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

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