Skip to main content
Log in

Impact of KIR/HLA ligand combinations on immune responses in malignant melanoma

  • Symposium Paper
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Tumor growth and dissemination depend partly on the reactivity of natural killer (NK) cells and T cells expressing NK-associated receptors. Their effector functions are regulated by an array of activating and inhibitory cell surface receptors with MHC class I ligand specificity, such as the killer immunoglobulin-like receptors (KIRs). Given the extensive genomic diversity of KIRs and their HLA ligands, it is reasonable to speculate that HLA, KIR gene variations and specific KIR-ligand combinations will have an impact on disease susceptibility and/or progression. Here, we discuss how KIR genotypes and KIR/HLA immunogenetic profiles may be involved in tumorigenesis, especially in malignant melanoma (MM). A hypothetical model of the impact of KIR/ligand combinations on immune responses in MM is proposed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Algarra I, Garcia-Lora A, Cabrera T, Ruiz-Cabello F, Garrido F (2004) The selection of tumor variants with altered expression of classical and nonclassical MHC class I molecules: implications for tumor immune escape. Cancer Immunol Immunother 53:904–910

    Article  PubMed  CAS  Google Scholar 

  2. Amheim L, Dillner J, Sanjeevi CB (2005) A population based cohort study of KIR genes and genotypes in relation to cervical intraepithelial neoplasia. Tissue Antigens 65:252–259

    Article  CAS  Google Scholar 

  3. Bateman AC, Turner SJ, Theaker JM, Howell WM (1998) HLA-DQB1*0303 and *0301 alleles influence susceptibility to and prognosis in cutaneous malignant melanoma in the British Caucasian population. Tissue Antigens 52:67–73

    PubMed  CAS  Google Scholar 

  4. Bettinotti MP, Norris RD, Hackett JA, Thompson CO, Simonis TB, Stroncek D, Marincola FM (2000) Frequency of human leukocyte antigen-A24 alleles in patients with melanoma determined by human leukocyte antigen-A sequence-based typing. J Immunother 23:282–287

    Article  PubMed  CAS  Google Scholar 

  5. Biassoni R, Falco M, Cambiaggi A, Costa S, Verdiani S, Pende D, Conte R, et al (1995) Amino acid substitutions can influence the natural killer (NK)-mediated recognition of HLA-C molecules. Role of serine-77 and lysine-80 in the target cell protection from lysis mediated by “group 2” or “group 1” NK clones. J Exp Med 182:605–609

    Article  PubMed  CAS  Google Scholar 

  6. Biassoni R, Cantoni C, Falco M, Verdiani S, Bottino C, Vitale M, Conte R, Poggi A, Moretta A, Moretta L (1996) The human leucocyte antigen (HLA)-C-specific ‘activatory’ or ‘inhibitory’ natural killer cell receptors display highly homologous extracellular ddomains but differ in their transmembrane and intracytoplasmic portions. J Exp Med 183:645–650

    Article  PubMed  CAS  Google Scholar 

  7. Biassoni R, Pessino A, Malaspina A, Cantoni C, Bottino C, Sivori S, Moretta L, Morreta A (1997) Role of amino acid position 70 in the binding affinity of p50.1 and p58.1 receptors for HLA-Cw4 molecules. Eur J Immunol 27:3095–3099

    PubMed  CAS  Google Scholar 

  8. Burnet FM (1967) Immunological aspects of malignant disease. Lancet 1:1171–1174

    Article  PubMed  CAS  Google Scholar 

  9. Campillo JA, Martinez-Escribano JA, Muro M, Moya-Quiles R, Marin LA, Montes-Ares O, Guerra N, et al (2005) HLA class I and class II frequencies in patients with cutaneous malignant melanoma from southeastern Spain: the role of HLA-C in disease prognosis. Immunogenetics 20:1–8

    Google Scholar 

  10. Carrington M, Wang S, Martin MP, Gao X, Schiffman M, Cheng J, Herrero R, et al (2005) Hierarchy of resistance to cervical neoplasia mediated by combinations of killer immunoglobulin-like receptor and human leukocyte antigen loci. JEM 201:106–1075

    Google Scholar 

  11. Cella M, Longo A, Ferrara GB, Strominger JL, Colonna M (1994) NK3-specific natural killer cells are selectively inhibited by Bw4-positive HLA alleles with isoleucine 80. J Exp Med 180:1235–1242

    Article  PubMed  CAS  Google Scholar 

  12. Crum KA, Logue SE, Curran MD, Middleton D (2000) Development of a PCR-SSOP approach capable of defining inhibitory receptor (KIR) gene sequence repertoire. Tissue Antigens 56:313–326

    Article  PubMed  CAS  Google Scholar 

  13. Gumperz JE, Litwin V, Philips JH, Lanier LL, Parham P (1995) The Bw4 public epitope of HLA-B molecules confers reactivity with natural killer cell clones that express NKB1, a putative HLA receptor. J Exp Med 181:1133–1144

    Article  PubMed  CAS  Google Scholar 

  14. Hsu KC, Keever-Taylor CA, Wilton A, Pinto C, Heller G, Arkun K, O’Reilly RJ, et al (2005) Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes. Blood 105:4878–4884

    Article  PubMed  CAS  Google Scholar 

  15. Jager MJ, Volker-Dieben HJ, de Wolff-Rouendaal D, Kakebeeke-Kemme H, D’Amaro J (1992) Possible relation between HLA and ABO type and prognosis of uveal melanoma. Doc Ophthalmol 82:43–47

    Article  PubMed  CAS  Google Scholar 

  16. Kageshita T, Naruse T, Hirai S, Ono T, Horikoshi T, Nakagawa H, Tamaki K, et al (1997) Molecular genetics analysis of HLA class II alleles in Japanese patients with melanoma. Tissue Antigens 49:466–470

    Article  PubMed  Google Scholar 

  17. Katz G, Markel G, Mizrahi S, Arnon TI, Mandelboim O (2001) Recognition of HLA-Cw4 but not HLA-Cw6 by the NK cell receptor killer cell Ig-like receptor two-domain short tail number 4. J Immunol 166:7260–7267

    PubMed  CAS  Google Scholar 

  18. Katz G, Gazit R, Arnon TI, Gonen-Gross T, Tarcic G, Markel G, Gruda R, et al (2004) MHC class I-independent recognition of NK-activating receptor KIR2DS4. J Immunol 173:1819–1825

    PubMed  CAS  Google Scholar 

  19. Lee JE, Reveille JD, Ross MI, Platsoucas CD (1994) HLA-DQB1*0301 association with increased cutaneous melanoma risk. Int J Cancer 59:510–513

    PubMed  CAS  Google Scholar 

  20. Lee JE, Lu M, Mansfield PF, Platsoucas CD, Reveille JD, Ross MI (1996) Malignant melanoma: relationship of HLA class II gene DQB1*0301 to decreased recurrence in AJCC on cancer stage I or II. Cancer 78:758–763

    Article  PubMed  CAS  Google Scholar 

  21. Lee JE, Abdalla J, Porter GA, Bradford L, Grimm EA, Reveille JD, Mansfield PF, et al (2002) Presence of the human leucocyte antigen class II gene DRB1*1101 predicts interferon γ levels and disease recurrence in melanoma patients. Ann Surg Oncol 9:587–593

    Article  PubMed  Google Scholar 

  22. Lombardi ML, Mercuro O, Pirozzi G, Ionna F, Lombari V, Mozzillo N, Manzo C (1998) Molecular analysis of HLA-DRB1 and -DQB1 polymorphism in Italian melanoma patients. J Immunotherapy 21:435–439

    Article  CAS  Google Scholar 

  23. Lulli P, Grammatico P, Brioli G, Catricala C, Morellini M, Roccella M, Mariani B, et al (1998) HLA-DR and -DQ alleles in Italian patients with melanoma. Tissue Antigens 51:276–280

    Article  PubMed  CAS  Google Scholar 

  24. Mandelboim O, Reyburn HT, Vales-Gomez M, Pazmany L, Colonna M, Borsellino G, Strominger JL (1996) Protection from lysis by natural killer cells of group 1 and 2 specificity is mediated by residue 80 in human histocompatibility leukocyte antigen C alleles and also occurs with empty major histocompatibility complex molecules. J Exp Med 184:913–922

    Article  PubMed  CAS  Google Scholar 

  25. Naumova E, Ivanova M (2004) Putative molecular model of HLA associated autoimmune diseases in the Bulgarian population. Modern Medicine (BG) 4:45–52

    Google Scholar 

  26. Naumova E, Mihaylova A, Stoitchkov K, Ivanova M, Quin L, Toneva M (2005) Genetic polymorphism of NK receptors and their ligands in melanoma patients: prevalence of inhibitory over activating signals. Cancer Immunol Immunother 54:172–178

    Article  PubMed  CAS  Google Scholar 

  27. Norman PJ, Stephens HAF, Verity DH, Chandanayingyong D, Vaughan RW (2001) Distribution of natural killer cell immunoglobulin-like receptor sequences in three ethnic groups. Immunogenetics 52:195–205

    Article  PubMed  CAS  Google Scholar 

  28. Parham P (2005) Immunogenetics of killer cell immunoglobulin-like receptors. Mol Immunol 42:459–462

    Article  PubMed  CAS  Google Scholar 

  29. Parham P (2005) MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol 5:201–214

    Article  PubMed  CAS  Google Scholar 

  30. Pawelec G (2004) Tumour escape: antitumour effectors too much of a good thing?. Cancer Immunol Immunother 53:262–274

    Article  PubMed  CAS  Google Scholar 

  31. Pellegris G, Illeni MT, Vaglini M, Rovini D, Cascinelli N, Masserini C (1980) HLA antigens in malignant melanoma patients. Tumori 66:51–58

    Article  PubMed  CAS  Google Scholar 

  32. Rajalingam R (2002) Diversity of NK cell receptors and their HLA class I ligands. ASHI Quarterly 26:68–72

    Google Scholar 

  33. Rajagopalan S, Long EO (2005) Understanding how combinations of HLA and KIR genes influence disease. JEM 201:1025–1029

    Article  CAS  Google Scholar 

  34. Steward CA, Langier-Anfossi F, Vély F, Saulquin X, Riedmuller J, Tisserant A, Gauthier L, et al (2005) Recognition of peptide-MHC class I complexes by activating killer immunoglobulin-like receptors. PNAS 102:13224–13229

    Article  CAS  Google Scholar 

  35. Tarazona R, Casado JG, Soto R, DelaRosa O, Peralbo E, Rioja L, Pena J, Solana R (2004) Expression of NK-associated receptors on cytotoxic T cells from melanoma patients: a two-edged sword? Cancer Immunol Immunother 53:911–924

    Article  PubMed  CAS  Google Scholar 

  36. Trowsdale J (2001) Genetic and functional relationships between MHC and NK receptor genes. Immunity 15:363–374

    Article  PubMed  CAS  Google Scholar 

  37. Velardi A, Ruggeri L, Moretta A, Moretta L (2002) NK cells: a lesson from mismatched hematopoietic transplantation. Trends Immunol 23:438–444

    Article  PubMed  CAS  Google Scholar 

  38. Witt CS, Dewing C, Sayer DC, Uhrberg M, Parham P, Christiansen FT (1999) Population frequencies and putative haplotypes of the killer cell immunoglobulin-like receptor sequences and evidence for recombination. Transplantation 68:1784–1789

    Article  PubMed  CAS  Google Scholar 

  39. Yeager M, Hughes A (1999) Evolution of the mammalian MHC: natural selection, recombination, and convergent evolution. Immunological Reviews 167:45–59

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by research grants from the ENACT (LSHC-CT-2004-503306) and ESTDAB (QLRT-2000-01325) EC projects. The authors thank professor Graham Pawelec for critical reading of the manuscript and valuable advices.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elissaveta Naumova.

Additional information

This article is a symposium paper from the conference “Progress in Vaccination against Cancer 2005 (PIVAC 5)”, held in Athens, Greece, on 20–21 September 2005.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Naumova, E., Mihaylova, A., Ivanova, M. et al. Impact of KIR/HLA ligand combinations on immune responses in malignant melanoma. Cancer Immunol Immunother 56, 95–100 (2007). https://doi.org/10.1007/s00262-006-0151-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-006-0151-9

Keywords

Navigation