Abstract

Class II HLA antigens comprise the gene products of the HLA-DR, DQ and DP loci. These antigens have a restricted tissue distribution and mediate cell-cell interactions required to generate immune responses. Studies with a limited number of patients have shown that the level of expression of Class II HLA antigens in metastases from patients with melanoma is associated with the clinical course of the disease. After having confirmed this association on a large number of patients and with long periods of follow-up, this study will analyze immunological events as mechanisms underlying the role of Class II HLA antigens in the clinical course of melanoma. Specifically utilizing serological and immunochemical assays we will characterize primary and metastatic lesions for their expression of HLA-DR, DQ and DP antigens and we will analyze their effect on the degree of inflammatory response and on the phenotype of infiltrating cells. Furthermore we will characterize the role of HLA-DR, DQ and DP antigens i) in the proliferation of T cells stimulated with autologous melanoma cells isolated fromprimary and metastatic lesions and ii) in the immunogenicity of melanoma associated antigens recognized by monoclonal antibodies. The results of these studies in conjunction with information about the clinical course of the disease will assess the role of Class II HLA antigens in the biology of melanoma cells and the clinical significance of the detection of Class II HLA antigens on melanoma cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA039559-02
Application #
3178692
Study Section
Immunobiology Study Section (IMB)
Project Start
1986-06-01
Project End
1989-05-31
Budget Start
1987-06-01
Budget End
1988-05-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
New York Medical College
Department
Type
Schools of Medicine
DUNS #
City
Valhalla
State
NY
Country
United States
Zip Code
10595

  Publications

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Takamiya, Y; Schonbach, C; Nokihara, K et al. (1994) HLA-B*3501-peptide interactions: role of anchor residues of peptides in their binding to HLA-B*3501 molecules. Int Immunol 6:255-61
Kageshita, T; Kimura, T; Yoshi, A et al. (1994) Antigenic profile of mucosal melanoma lesions. Int J Cancer 56:370-4
Gattoni-Celli, S; Calorini, L; Byers, H R et al. (1993) Abnormalities in HLA class I antigen expression by melanoma cells: structural characterization and functional implications. J Invest Dermatol 100:226S-230S
Kageshita, T; Wang, Z; Calorini, L et al. (1993) Selective loss of human leukocyte class I allospecificities and staining of melanoma cells by monoclonal antibodies recognizing monomorphic determinants of class I human leukocyte antigens. Cancer Res 53:3349-54
Wang, Z; Cao, Y; Albino, A P et al. (1993) Lack of HLA class I antigen expression by melanoma cells SK-MEL-33 caused by a reading frameshift in beta 2-microglobulin messenger RNA. J Clin Invest 91:684-92
Kageshita, T; Kuriya, N; Ono, T et al. (1993) Association of high molecular weight melanoma-associated antigen expression in primary acral lentiginous melanoma lesions with poor prognosis. Cancer Res 53:2830-3
Gattoni-Celli, S; Byers, R H; Calorini, L et al. (1993) Organ-specific metastases in melanoma: experimental animal models. Pigment Cell Res 6:381-4
Wang, Z; Hu, X Z; Tatake, R J et al. (1993) Differential effect of human and mouse beta 2-microglobulin on the induction and the antigenic profile of endogenous HLA-A and -B antigens synthesized by beta 2-microglobulin gene-null FO-1 melanoma cells. Cancer Res 53:4303-9
Gattoni-Celli, S; Calorini, L; Simile, M M et al. (1993) Modulation by MHC class I antigens of the biology of melanoma cells. Non-immunological mechanisms. Melanoma Res 3:285-9

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