Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Targeted therapy of solid malignancies via HLA class II antigens: a new biotherapeutic approach?

Oncogene volume 22, pages 6564–6569 (2003)Cite this article

Abstract

Intracellular signals, delivered in professional antigen-presenting cells following the engagement of major histocompatibility complex (MHC) class II molecules, activate a variety of cellular functions that also contribute to efficient antigen presentation. As far as human malignancies, the signaling ability of human leukocyte antigens (HLA) class II molecules is a rather well-characterized event in hematologic tumors; in contrast, very limited evidences are available in solid neoplasias of different histotypes that may constitutively express HLA class II antigens. Among solid malignancies, a significant proportion of human cutaneous melanomas have been shown to express HLA class II molecules, and cutaneous melanoma undoubtedly represents a ‘model disease’ to investigate tumor immunobiology, to unveil the molecular basis underlying the interactions between neoplastic cells and host's immune system, and ultimately to set up new bio-immunotherapeutic approaches. Upcoming preclinical evidences unveil a signaling potential of HLA-DR antigens expressed on melanoma cells, and suggest for the clinical implication of HLA class II molecules as novel therapeutic targets. Therefore, in this review, we will focus on the emerging role of HLA class II antigens as intracellular signal transducing elements in neoplastic cells of the melanocytic lineage, emphasizing their foreseeable role in targeted therapy of human melanoma and potentially of HLA class II antigens-positive tumors of different histology.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

Abbreviations

APC:

antigen-presenting cells

CIITA:

Class II transactivator protein

HLA:

human leucocyte antigens

FAK:

focal adhesion kinase

MHC:

major histocompatibility complex

mAb:

monoclonal antibody

NB:

neuroblastoma

TAA:

tumor-associated antigen

SCLC:

small cell lung carcinoma

References

  • Albino AP, Houghton AN, Eisinger M, Lee JS, Kantor RR, Oliff AI and Old LJ . (1986). J. Exp. Med., 164, 1710–1722.

  • Altomonte M, Pucillo C, Damante G and Maio M . (1993). J. Immunol., 151, 5115–5122.

  • Altomonte M, Pucillo C and Maio M . (1999). J. Cell. Physiol., 179, 251–256.

  • Altomonte M, Visintin A, Tecce R, Pucillo C and Maio M . (2003). J. Cell. Physiol., in press.

  • Andrè P, Cambier JC, Wade TK, Raetz T and Wade WF . (1994). J. Exp. Med., 179, 763–768.

  • Angelisova P, Hilgert I and Horejsi V . (1994). Immunogenetics, 39, 249–256.

  • Bartek J, Petrek M, Vojtesek B, Bartkova J, Kovarik J and Rejthar A . (1987). Br. J. Cancer, 56, 727–733.

  • Bernard D, Maurizis JC, Ruse F, Chassagne J, Chollet P, Sauvezie B, de Latour M and Plagne R . (1984). Clin. Exp. Immunol., 56, 215–221.

  • Bernsen MR, Hakansson L, Gustafsson B, Krysander L, Rettrup B, Ruiter D and Hakansson A . (2003). Br. J. Cancer, 88, 424–431.

  • Brasanac D, Markovic-Lipkovski J, Hadzi-Djokic J, Muller GA and Muller CA . (1999). Neoplasma, 46, 173–178.

  • Brunner CA, Gokel JM, Riethmüller G and Johnson JP . (1991). Eur. J. Cancer, 27, 411–416.

  • Byrne SN and Halliday GM . (2003). Cancer Immunol. Immunother., 52, 396–402.

  • Cabrera T, Ruiz-Cabello F and Garrido F . (1995). Scand. J. Immunol., 41, 398–406.

  • Chang CH and Flavell RA . (1995). J. Exp. Med., 181, 765–767.

  • Chang ES and Sohn SS . (1995). J. Korean Med. Sci., 10, 334–341.

  • Chia CP, Khrebtukova I, McCluskey J and Wade WF . (1994). J. Immunol., 153, 3398–3407.

  • Chin KC, Mao C, Skinner C, Riley JL, Wright KL, Moreno CS, Stark GR, Boss JM and Ting JP . (1995). Immunity, 1, 687–697.

  • Concha A, Esteban F, Cabrera T, Ruiz-Cabello F and Garrido F . (1991). Semin. Cancer Biol., 2, 47–54.

  • Coral S, Pucillo C, Leonardi A, Fonsatti E, Altomonte M and Maio M . (1997). Cell Growth Differ., 8, 581–588.

  • Dechant M, Vidarsson G, Stockmeyer B, Repp R, Glennie MJ, Gramatzki M, van De Winkel JG and Valerius T . (2002). Blood, 100, 4574–4580.

  • Esteban F, Concha A, Huelin C, Pérez-Ayala M, Pedrinacci S, Ruiz-Cabello F and Garrido F . (1989). Int. J. Cancer, 43, 436–442.

  • Feinmesser M, Sulkes A, Morgenstern S, Sulkes J, Stern S and Okon E . (2000). J. Clin. Pathol., 53, 286–291.

  • Garban F, Truman JP, Lord J, Drénou B, Plumas J, Jacob MC, Sotto JJ, Charron D and Mooney N . (1998). Exp. Hematol., 26, 874–884.

  • Glew SS, Duggan-Keen M, Cabrera T and Stern PL . (1992). Cancer Res., 52, 4009–4016.

  • Goodwin BL, Xi H, Tejiram R, Eason DD, Ghosh N, Wright KL, Nagarajan U, Boss JM and Blanck G . (2001). Cell Growth Differ., 12, 327–335.

  • Gutierrez J, López-Nevot MA, Cabrera T, Oliva R, Esquivias J, Ruiz-Cabello F and Garrido F . (1987). Expl. Clin. Immunogenet, 4, 144–152.

  • Harton JA, Van Hagen AE and Bishop GA . (1995). Immunity, 3, 349–358.

  • Heike M, Schlaak J, Schulze-Bergkamen H, Heyl S, Herr W, Schmitt U, Schneider PM and Meyer zum Buschenfelde KH . (1996). J. Immunol., 156, 2205–2213.

  • Hilders CGJM, Munoz IM, Nooyen Y and Fleuren GJ . (1995). Gynecol. Oncol. Jun., 57, 366–375.

  • Hilton DA and West KP . (1990). Cancer, 15, 1154–1157.

  • Houck JR, Sexton FM and Zajdel G . (1990). Arch. Otolaryngol. Head Neck Surg., 116, 1181–1185.

  • Hurlimann J and Saraga P . (1985). Int J. Cancer, 35, 753–762.

  • Ioachim E, Charchanti A, Stavropoulos NE, Skopelitou A, Athanassiou ED and Agnantis N . (2000). Histol. Histopathol., 15, 721–727.

  • Ishigami S, Aikou T, Natsugoe S, Hokita S, Iwashige H, Tokushige M and Sonoda S . (1998). Oncology, 55, 65–69.

  • Kern I, Steimle V, Siegrist CA and Mach B . (1995). Int. Immunol., 7, 1295–1299.

  • Koretz K, Moldenhauer G, Majdic O and Möller P . (1989). Int. J. Cancer., 44, 816–822.

  • Kunihiro M, Tanaka S, Haruma K, Yoshihara M, Sumii K, Kajiyama G and Shimamoto F . (1998). Oncology, 55, 326–333.

  • Laufer TM, Smiley ST, Ranger A, Clements VK, Ostrand-Rosenberg S and Glimcher LH . (1997). J. Immunol., 159, 5914–5920.

  • Lazaris AC, Theodoropoulos GE, Davaris PS, Panoussopoulos D, Nakopoulou L, Kittas C and Golematis Basil C . (1995). Dis. Colon Rectum, 38, 739–745.

  • Lazzaro B, Anderson AE, Kajdacsy-Balla A and Hessner MJ . (2001). Appl. Immunohistochem., 9, 234–241.

  • Levy S, Todd SC and Maecker HT . (1998). Annu. Rev. Immunol., 16, 89–109.

  • Lovig T, Andersen SN, Thorstensen L, Diep CB, Meling GI, Lothe RA and Rognum TO . (2002). Br. J. Cancer, 87, 756–762.

  • Lu Y, Tschickardt ME, Schmidt BJ and Blanck G . (1997). Immunol. Cell Biol., 75, 325–332.

  • Lucin K, Internicka Z and Joniic N . (1994). Pathol. Res. Pract., 190, 1134–1140.

  • Ma XC, Hattori T, Kushima R, Terata N and Kodama M . (1994). Acta Oncol., 33, 187–190.

  • Maio M, Gulwani B, Morgano A and Ferrone S . (1989). Int. J. Cancer, 44, 554–559.

  • Marsh SGE, Parham P and Barber LD . (2000). The HLA FactsBook. Academic Press: London, pp. 26–36.

    Book  Google Scholar 

  • Mattijssen V, De Mulder PHM, Schalkwijk L, Manni JJ, Van't Hof-Grootenboer B and Ruiter DJ . (1991). Int. J. Cancer, (Suppl) 6, 95–100.

  • Möller P, Mattfeldt T, Gross C, Schlosshauer P, Koch A, Koretz K, Moldenhauer G, Kaufmann M and Otto HF . (1989). Am. J. Pathol., 135, 73–83.

  • Morita M, Tanaka K, Kawanishi H, Tsuji M, Ookusa T, Takada H, Okamura A and Hioki K . (1995). J. Surg. Oncol., 59, 233–238.

  • Muhlethaler-Mottet A, Otten LA, Steimle V and Mach B . (1997). EMBO J., 16, 2851–2860.

  • Nabavi N, Freeman GJ, Gault A, Godfrey D, Nadler LM and Glimcher LH . (1992). Nature, 360, 266–268.

  • Nagy ZA, Huber B, Loaning C, Rauchenberger R, Reiffert S, Thomassen-Wolf E, Zahn S, Leyer S, Schier EM, Zahradnik A, Brunner C, Lobenwein K, Rattel B, Stanglmaier M, Hallek M, Wing M, Anderson S, Dunn M, Kretzschmar T and Tesar M . (2002). Nat. Med., 8, 801–807.

  • Natali PG, Giacomini P, Bigotti A, Imai K, Nicotra MR, Ng AK and Ferrone S . (1983). Cancer Res., 43, 660–668.

  • Norheim Andersen S, Rognum TO, Lund E, Meling GI and Hauge S . (1993). Br. J. Cancer, 68, 80–85.

  • Ostmeier H, Fuchs B, Otto F, Mawick R, Lippold A, Krieg V and Suter L . (1999). Cancer, 85, 2391–2399.

  • Ostmeier H, Fuchs B, Otto F, Mawick R, Lippold A, Krieg V and Suter L . (2001). Br. J. Dermatol., 145, 203–209.

  • Perez M, Cabrera T, Lopez Nevot MA, Gomez M, Peran F, Ruiz-Cabello F and Garrido F . (1986). J. Immunogenet., 13, 247–253.

  • Piskurich JF, Linhoff MW, Wang Y and Ting JP . (1999). Mol. Cell. Biol., 19, 431–440.

  • Piskurich JF, Wang Y, Linhoff MW, White LC and Ting JP . (1998). J. Immunol., 160, 233–240.

  • Reith W and Mach B . (2001). Annu. Rev. Immunol., 19, 331–373.

  • Renkvist N, Castelli C, Robbins PF and Parmiani G . (2001). Cancer Immunol. Immunother., 50, 3–15.

  • Ricaniadis N, Kataki A, Agnantis N, Androulakis G and Karakousis CP . (2001). Eur. J. Surg. Oncol., 27, 88–93.

  • Rognum TO, Brandtzaeg P and Thorud E . (1983). Br. J. Cancer, 48, 543–551.

  • Rubinstein E, Le Naour F, Lagaudriere-Gesbert C, Billard M, Conjeaud H and Boucheix C . (1996). Eur. J. Immunol., 26, 2657–2665.

  • Sadanaga N, Kuwano H, Watanabe M, Maekawa S, Mori M and Sugimachi K . (1994). Cancer, 74, 586–591.

  • Saito T, Kimura M, Kawasaki T, Sato S and Tomita Y . (1997). Cancer Lett., 115, 121–127.

  • Schick MR and Levy S . (1993). J. Immunol., 151, 4090–4097.

  • Scholl PR and Geha RS . (1994). Immunol. Today, 15, 418–422.

  • Schwab M, Shimada H, Joshi V and Brodeur GM . (2000). Pathology and Genetics of Tumours of the Nervous System. Kleihues P, Cabenee WK (eds). International Agency for Research on cancer: Lyon, pp. 153–161.

    Google Scholar 

  • Si Z and Hersey P . (1993). Int. J. Cancer., 54, 37–43.

  • Steimle V, Otten LA, Zufferey M and Mach B . (1993). Cell, 75, 135–146.

  • Steimle V, Siegrist CA, Mottet A, Lisowska-Grospierre B and Mach B . (1994). Science, 265, 106–109.

  • Stockmeyer B, Schiller M, Repp R, Lorenz HM, Kalden JR, Gramatzki M and Valerius T . (2002). Br. J. Haematol., 118, 959–967.

  • St-Pierre Y, Nabavi N, Ghogawala Z, Glimcher LH and Watts TH . (1989). J Immunol., 143, 808–812.

  • Sumiyoshi K, Kuwano H, Watanabe M, Kitamura M, Toh Y and Sugimachi K . (1999). Oncol. Rep., 6, 301–306.

  • Szollosi J, Horejsi V, Bene L, Angelisova P and Damjanovich S . (1996). J. Immunol., 157, 2939–2946.

  • Taramelli D, Fossati G, Mazzocchi A, Delia D, Ferrone S and Parmiani G . (1986). Cancer Res., 46, 433–439.

  • Tatsumi T, Kierstead LS, Ranieri E, Gesualdo L, Schena FP, Finke JH, Bukowski RM, Brusic V, Sidney J, Sette A, Logan TF, Kasamon YL, Slingluff Jr CL, Kirkwood JM and Storkus WJ . (2003). Clin. Cancer Res., 9, 947–954.

  • Ting JP, Wright KL, Chin KC, Brickey WJ and Li G . (1997). J. Immunol., 159, 5457–5462.

  • Trieb K, Lechleitner T, Lang S, Windhager R, Kotz R and Dirnhofer S . (1998). Pathol. Res. Pract., 194, 679–684.

  • Truman JP, Choqueux C, Charron D and Mooney N . (1996a). Cell. Immunol., 172, 149–157.

  • Truman JP, Garban F, Choqueux C, Charron D and Mooney N . (1996b). Exp. Hematol., 24, 1409–1415.

  • van der Stoep N, Biesta P, Quinten E and van den Elsen PJ . (2002). Int. J. Cancer, 97, 501–507.

  • van Duinen SG, Ruiter DJ, Broecker EB, van der Velde EA, Sorg C, Welvaart K and Ferrone S . (1988). Cancer Res., 48, 1019–1025.

  • Vora AR, Rodgers S, Parker AJ, Start R, Rees RC and Murray AK . (1997). Br. J. Cancer, 76, 836–844.

  • Wade WF, Davoust J, Salamero J, Andre P, Watts TH and Cambier JC . (1993). Immunol. Today, 14, 539–546.

  • Westerheide SD, Louis-Plence P, Ping D, He XF and Boss JM . (1997). J. Immunol., 158, 4812–4821.

  • Wintzer HO, Benzing M and von Kleist S . (1990). Br. J. Cancer, 62, 289–295.

  • Yazawa T, Ito T, Kamma H, Suzuki T, Okudela K, Hayashi H, Horiguchi H, Ogata T, Mitsui H, Ikeda M and Kitamura H . (2002). Am. J. Pathol., 161, 291–300.

  • Yazawa T, Kamma H, Fujiwara M, Matsui M, Horiguchi H, Satoh H, Fujimoto M, Yokoyama K and Ogata T . (1999). J. Pathol., 187, 191–199.

  • Yazawa T, Kamma H and Ogata T . (1993). Appl. Immunohistochem., 1, 289–296.

  • Zuk JA and Walker RA . (1987). J. Pathol., 152, 275–285.

  • Zuk JA and Walker RA . (1988). J. Pathol., 155, 301–309.

Download references

Acknowledgements

This work was supported by the Associazione Italiana Ricerca sul Cancro and by the Progetto Ricerca Finalizzata awarded by the Italian Ministry of Public Health. We acknowledge the skilful editorial assistance of Dr Anna D'Amato.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Cancer Bioimmunotherapy Unit, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico, via Pedemontana Occ. le, 12, Aviano, 33081, Italy

    Maresa Altomonte, Ester Fonsatti, Alberto Visintin & Michele Maio

Authors
  1. Maresa Altomonte
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ester Fonsatti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alberto Visintin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michele Maio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maresa Altomonte.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Altomonte, M., Fonsatti, E., Visintin, A. et al. Targeted therapy of solid malignancies via HLA class II antigens: a new biotherapeutic approach?. Oncogene 22, 6564–6569 (2003). https://doi.org/10.1038/sj.onc.1206960

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206960

Keywords

This article is cited by

Search

Advanced search

Quick links