Augmentation of NK cell-mediated cytotoxicity to tumor cells by inhibitory NK cell receptor blockers

Tajima, Kyoko; Matsumoto, Naoki; Ohmori, Kazuji; Wada, Haruka; Itô, Masayuki; Suzuki, Kazuhiro; Yamamoto, Kazuo

doi:10.1093/intimm/dxh021

Cited by 13 publications

(11 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Blocking of MHC class I on Sezary cell lines and fresh Sezary cells, however, enhances or induces their susceptibility to NK lysis, indicating that MHC class I on the malignant target cells participate in their protection, as previously described for leukemic B cells (Palucka et al, 1998). Interestingly, it has been shown that inhibitory NK cell receptor blockers enhance NK cell-mediated killing of tumor cells that are otherwise resistant because of MHC class I expression (Tajima et al, 2004). Nevertheless, with both allogeneic and autologous combinations, we found that MHC class I molecule expression is not sufficient to prevent NK cell lysis completely.…”

Section: Discussionmentioning

confidence: 58%

Circulating Natural Killer Lymphocytes Are Potential Cytotoxic Effectors Against Autologous Malignant Cells in Sezary Syndrome Patients

Bouaziz¹,

Ortonne²,

Giustiniani³

et al. 2005

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Patients with advanced cutaneous T cell lymphoma (CTCL) exhibit profound defects in cell-mediated immunity. Although it has been suggested that Sezary syndrome (SS) patients have a decreased natural killer (NK) lymphocyte activity, nothing has been reported concerning the sensitivity of Sezary cells to NK lymphocyte-mediated cytotoxicity. Peripheral blood NK cells from healthy donors were tested against Sezary tumoral cell lines as well as against freshly isolated Sezary cells. Further, we studied their ability to exhibit antibody -dependent cell-mediated cytotoxicity using either the murine anti-CD158k/KIR3DL2 monoclonal antibody (moAb) AZ158 that specifically recognizes Sezary cells, or the anti-CD52 monoclonal antibody alemtuzumab. The results show that Sezary cell lines are susceptible to NK lymphocyte lysis. More importantly, we found that freshly isolated malignant cells are killed either by IL-2 activated allogeneic NK lymphocytes or when the tumor lymphocyte targets are incubated with an anti-MHC class I F(ab)'2 antibody. Further, anti-KIR3DL2 and anti-CD52 moAb can enhance the NK lysis. Finally, we report that NK lymphocytes isolated from SS patients are potentially cytotoxic lymphocytes against autologous malignant Sezary cells. These findings indicate that antitumor-mediated NK lymphocyte cytotoxic activity can be triggered in patients with CTCL and raise the possibility of developing novel therapeutic strategies by stimulating their innate immunity.

show abstract

Section: Discussionmentioning

confidence: 58%

Circulating Natural Killer Lymphocytes Are Potential Cytotoxic Effectors Against Autologous Malignant Cells in Sezary Syndrome Patients

Bouaziz¹,

Ortonne²,

Giustiniani³

et al. 2005

Journal of Investigative Dermatology

View full text Add to dashboard Cite

show abstract

“…It has also been observed in in vitro studies that a blockage of KIR markedly increases CTL-mediated killing of HIV-infected, autologous cells [40]. In mice, which do not have KIR genes but express their functional orthologs (LY49 genes) on their NK cells and a subset of CTL, it was also demonstrated that blockage of LY49 receptors increases anti-tumor activities of NK cells resulting in tumor regression [142,143]. Interestingly iKIR, CD94/NKG2, and KLR-G1 could also be detected but sparsely on CD4 ϩ T cells in human peripheral blood.…”

Section: Changing the Expression Of Nkrs On Non-nk Cellsmentioning

confidence: 94%

Antiviral NK cell responses in HIV infection: II. viral strategies for evasion and lessons for immunotherapy and vaccination

Iannello

Débbeche

Samarani

et al. 2008

Journal of Leukocyte Biology

View full text Add to dashboard Cite

As is the case in other viral infections, humans respond to HIV infection by activating their NK cells. However, the virus uses several strategies to neutralize and evade the host's NK cell responses. Consequently, it is not surprising that NK cell functions become compromised in HIV-infected individuals in early stages of the infection. The compromised NK cell functions also adversely affect several aspects of the host's antiviral adaptive immune responses. Researchers have made significant progress in understanding how HIV counters NK cell responses of the host. This knowledge has opened new avenues for immunotherapy and vaccination against this infection. In the first part of this review article, we gave an overview of our current knowledge of NK cell biology and discussed how the genes encoding NK cell receptors and their ligands determine innate genetic resistance/susceptibilty of humans against HIV infections and AIDS. In this second part, we discuss NK cell responses, viral strategies to counter these responses, and finally, their implications for anti-HIV immunotherapy and vaccination.

show abstract

“…One strategy to enhance NK cell activity is to block these inhibitory receptors and allow ‘missing-self’ recognition to occur. Studies using mAbs or small molecular weight inhibitors to block murine inhibitory Ly49 receptors or human killer-cell immunoglobulin-like receptors (KIR) showed the potential of generating anti-tumor immunity by releasing a brake on NK cell activity [19–23]. In certain conditions, such as a growing tumor, the expression of ligands for inhibitory receptors can be reduced, and the lack of inhibitory signals may allow activation of NK cells [24].…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Designing multivalent proteins based on natural killer cell receptors and their ligands as immunotherapy for cancer

Smits

Coupet

Godbersen

et al. 2016

Expert Opinion on Biological Therapy

View full text Add to dashboard Cite

Introduction Natural killer (NK) cells are an important component of the innate immune system that play a key role in host immunity against cancer. NK cell recognition and activation is based on cell surface receptors recognizing specific ligands that are expressed on many types of tumor cells. Some of these receptors are capable of activating NK cell function while other receptors inhibit NK cell function. Therapeutic approaches to treat cancer have been developed based on preventing NK cell inhibition or using NK cell receptors and their ligands to activate NK cells or T cells to destroy tumor cells. Areas covered This article describes the various strategies for targeting NK cell receptors and NK cell receptor ligands using multivalent proteins to activate immunity against cancer. Expert opinion: NK cell receptors work in synergy to activate NK cell effector responses. Effective anti-cancer strategies will need to not only kill tumor cells but must also lead to the destruction of the tumor microenvironment. Immunotherapy based on NK cells and their receptors has the capacity to accomplish this through triggering lymphocyte cytotoxicity and cytokine production.

show abstract

Augmentation of NK cell-mediated cytotoxicity to tumor cells by inhibitory NK cell receptor blockers

Cited by 13 publications

References 42 publications

Circulating Natural Killer Lymphocytes Are Potential Cytotoxic Effectors Against Autologous Malignant Cells in Sezary Syndrome Patients

Circulating Natural Killer Lymphocytes Are Potential Cytotoxic Effectors Against Autologous Malignant Cells in Sezary Syndrome Patients

Antiviral NK cell responses in HIV infection: II. viral strategies for evasion and lessons for immunotherapy and vaccination

Designing multivalent proteins based on natural killer cell receptors and their ligands as immunotherapy for cancer

Contact Info

Product

Resources

About