Unlicensed NK Cells Target Neuroblastoma Following Anti-GD2 Antibody Treatment

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2012 Aug 7

PMID 22863621

Citations 140

Authors

Nidale Tarek

Jean-Benoit Le Luduec

Meighan M Gallagher

Junting Zheng

Jeffrey M Venstrom

Elizabeth Chamberlain

Shakeel Modak

Glenn Heller

Bo Dupont

Nai-Kong V Cheung

Katharine C Hsu

Affiliations

Soon will be listed here.

Abstract

Survival outcomes for patients with high-risk neuroblastoma (NB) have significantly improved with anti-disialoganglioside GD2 mAb therapy, which promotes NK cell activation through antibody-dependent cell-mediated cytotoxicity. NK cell activation requires an interaction between inhibitory killer cell immunoglobulin-like receptors (KIRs) and HLA class I ligands. NK cells lacking KIRs that are specific for self HLA are therefore "unlicensed" and hyporesponsive. mAb-treated NB patients lacking HLA class I ligands for their inhibitory KIRs have significantly higher survival rates, suggesting that NK cells expressing KIRs for non-self HLA are mediating tumor control in these individuals. We found that, in the presence of mAb, both licensed and unlicensed NK cells are highly activated in vitro. However, HLA class I expression on NB cell lines selectively inhibited licensed NK cell activity, permitting primarily unlicensed NK cells to mediate antibody-dependent cell-mediated cytotoxicity. These results indicate that unlicensed NK cells play a key antitumor role in patients undergoing mAb therapy via antibody-dependent cell-mediated cytotoxicity, thus explaining the potent "missing KIR ligand" benefit in patients with NB.

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References

Yokoyama W, Kim S . Licensing of natural killer cells by self-major histocompatibility complex class I. Immunol Rev. 2006; 214:143-54. DOI: 10.1111/j.1600-065X.2006.00458.x. View

Romagne F, Andre P, Spee P, Zahn S, Anfossi N, Gauthier L . Preclinical characterization of 1-7F9, a novel human anti-KIR receptor therapeutic antibody that augments natural killer-mediated killing of tumor cells. Blood. 2009; 114(13):2667-77. PMC: 2756126. DOI: 10.1182/blood-2009-02-206532. View

Sivori S, Parolini S, Marcenaro E, Castriconi R, Pende D, Millo R . Involvement of natural cytotoxicity receptors in human natural killer cell-mediated lysis of neuroblastoma and glioblastoma cell lines. J Neuroimmunol. 2000; 107(2):220-5. DOI: 10.1016/s0165-5728(00)00221-6. View

Raffaghello L, Prigione I, Airoldi I, Camoriano M, Morandi F, Bocca P . Mechanisms of immune evasion of human neuroblastoma. Cancer Lett. 2005; 228(1-2):155-61. DOI: 10.1016/j.canlet.2004.11.064. View

Rubio V, Stuge T, Singh N, Betts M, Weber J, Roederer M . Ex vivo identification, isolation and analysis of tumor-cytolytic T cells. Nat Med. 2003; 9(11):1377-82. DOI: 10.1038/nm942. View

Vertuani S, De Geer A, Levitsky V, Kogner P, Kiessling R, Levitskaya J . Retinoids act as multistep modulators of the major histocompatibility class I presentation pathway and sensitize neuroblastomas to cytotoxic lymphocytes. Cancer Res. 2003; 63(22):8006-13. View

Hsu K, Liu X, Selvakumar A, Mickelson E, OReilly R, Dupont B . Killer Ig-like receptor haplotype analysis by gene content: evidence for genomic diversity with a minimum of six basic framework haplotypes, each with multiple subsets. J Immunol. 2002; 169(9):5118-29. DOI: 10.4049/jimmunol.169.9.5118. View

Anfossi N, Andre P, Guia S, Falk C, Roetynck S, Stewart C . Human NK cell education by inhibitory receptors for MHC class I. Immunity. 2006; 25(2):331-42. DOI: 10.1016/j.immuni.2006.06.013. View

Ciccone E, Pende D, Nanni L, Di Donato C, Viale O, Beretta A . General role of HLA class I molecules in the protection of target cells from lysis by natural killer cells: evidence that the free heavy chains of class I molecules are not sufficient to mediate the protective effect. Int Immunol. 1995; 7(3):393-400. DOI: 10.1093/intimm/7.3.393. View

10.

Lampson L, Fisher C . Weak HLA and beta 2-microglobulin expression of neuronal cell lines can be modulated by interferon. Proc Natl Acad Sci U S A. 1984; 81(20):6476-80. PMC: 391947. DOI: 10.1073/pnas.81.20.6476. View

11.

Bryceson Y, March M, Barber D, Ljunggren H, Long E . Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells. J Exp Med. 2005; 202(7):1001-12. PMC: 2213171. DOI: 10.1084/jem.20051143. View

12.

Beelen D, Ottinger H, Ferencik S, Elmaagacli A, Peceny R, Trenschel R . Genotypic inhibitory killer immunoglobulin-like receptor ligand incompatibility enhances the long-term antileukemic effect of unmodified allogeneic hematopoietic stem cell transplantation in patients with myeloid leukemias. Blood. 2004; 105(6):2594-600. DOI: 10.1182/blood-2004-04-1441. View

13.

Delgado D, Hank J, Kolesar J, Lorentzen D, Gan J, Seo S . Genotypes of NK cell KIR receptors, their ligands, and Fcγ receptors in the response of neuroblastoma patients to Hu14.18-IL2 immunotherapy. Cancer Res. 2010; 70(23):9554-61. PMC: 2999644. DOI: 10.1158/0008-5472.CAN-10-2211. View

14.

Wu L, Parton A, Lu L, Adams M, Schafer P, Bartlett J . Lenalidomide enhances antibody-dependent cellular cytotoxicity of solid tumor cells in vitro: influence of host immune and tumor markers. Cancer Immunol Immunother. 2010; 60(1):61-73. PMC: 11029172. DOI: 10.1007/s00262-010-0919-9. View

15.

Beziat V, Descours B, Parizot C, Debre P, Vieillard V . NK cell terminal differentiation: correlated stepwise decrease of NKG2A and acquisition of KIRs. PLoS One. 2010; 5(8):e11966. PMC: 2917352. DOI: 10.1371/journal.pone.0011966. View

16.

Neal Z, Imboden M, Rakhmilevich A, Kim K, Hank J, Surfus J . NXS2 murine neuroblastomas express increased levels of MHC class I antigens upon recurrence following NK-dependent immunotherapy. Cancer Immunol Immunother. 2003; 53(1):41-52. PMC: 11032988. DOI: 10.1007/s00262-003-0435-2. View

17.

Venstrom J, Zheng J, Noor N, Danis K, Yeh A, Cheung I . KIR and HLA genotypes are associated with disease progression and survival following autologous hematopoietic stem cell transplantation for high-risk neuroblastoma. Clin Cancer Res. 2009; 15(23):7330-4. PMC: 2788079. DOI: 10.1158/1078-0432.CCR-09-1720. View

18.

Kim S, Poursine-Laurent J, Truscott S, Lybarger L, Song Y, Yang L . Licensing of natural killer cells by host major histocompatibility complex class I molecules. Nature. 2005; 436(7051):709-13. DOI: 10.1038/nature03847. View

19.

Wolint P, Betts M, Koup R, Oxenius A . Immediate cytotoxicity but not degranulation distinguishes effector and memory subsets of CD8+ T cells. J Exp Med. 2004; 199(7):925-36. PMC: 2211884. DOI: 10.1084/jem.20031799. View

20.

Yu J, Heller G, Chewning J, Kim S, Yokoyama W, Hsu K . Hierarchy of the human natural killer cell response is determined by class and quantity of inhibitory receptors for self-HLA-B and HLA-C ligands. J Immunol. 2007; 179(9):5977-89. DOI: 10.4049/jimmunol.179.9.5977. View