This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pandolfi, F. Articles by Gattoni-Celli, S. Search for Related Content PubMed PubMed Citation Articles by Pandolfi, F. Articles by Gattoni-Celli, S.

Expression of HLA-A2 Antigen in Human Melanoma Cell Lines and its Role in T-Cell Recognition¹

Department of Pathology [F. P., L. A. B., L. T., J. T. K.] and Cancer Center [K. J. I., S. G-C.], Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129

Previous studies have suggested that, in human melanoma, expression of HLA-A2 antigen is important for tumor cell recognition by autologous T-lymphocytes. Because of the recent demonstration that expression of HLA Class I antigens may be selectively lost in several human tumors, including melanoma, we derived pairs of tumor infiltrating lymphocytes (TIL) and melanoma cell lines from 4 human lymphocytic antigen (HLA)-A2⁺ patients with metastatic melanoma. We observed that, although all 4 TIL cultures expressed HLA-A2 antigen, only 2 melanoma cell lines did so. Melanoma cells derived from the other 2 patients showed neither surface expression of the HLA-A2 antigen nor presence of the corresponding mRNA. We also observed some correlation between loss of HLA-A2 expression and level of c-myc transcription. TIL derived from patients whose melanoma cell lines had normal expression of HLA-A2 had a CD8 phenotype and were capable of lysing autologous melanoma cells. Melanoma cell killing was CD3 and major histocompatibility complex Class I restricted in both cases, but HLA-A2 restricted in only one case. On the other hand, TIL derived from the 2 patients whose melanoma cell lines had lost expression of HLA-A2 had a predominant CD4 phenotype and virtually no cytotoxic activity. Preincubation of the HLA-A2 negative melanoma cell lines with - or -interferon did not induce the re-expression of the HLA-A2 antigen. In an attempt to restore HLA-A2 antigen expression in one of the melanoma cell lines that were HLA-A2 negative, we transfected these cells with the HLA-A2 gene subcloned in the pSV2-neo vector. Four transfected clones, with high levels of HLA-A2 antigen expression, were expanded and characterized. Proliferative and cytotoxic activities of TIL against the autologous transfected clones as well as the untransfected parental melanoma cell line were measured and compared. CD4⁺ TIL showed no difference in the proliferative response to autologous parental and HLA-A2 transfected clones. However, we observed selective recognition of the HLA-A2 expressing clones by autologous cultured peripheral blood lymphocytes (which contained CD8 cells) as well as allogeneic CD8⁺ TIL with a HLA-A2 restricted pattern of recognition. In contrast, virtually no cytotoxic activity was detected against either parental or HLA-A2 transfected clones. Overall, our data suggest that selective down-regulation of HLA-A2 antigen expression in melanoma cells may represent one of the mechanisms by which tumor cells escape immunological recognition.

¹ This work was supported in part by NIH Grants CA 44324, AR 39993, and DK 36350, American Cancer Society Institutional Grant 90-1008, and the North Atlantic Treaty Organization (NATO).

² To whom requests for reprints should be addressed, at Massachusetts General Hospital Pathology Research, 149 Thirteenth Street, Charlestown, MA 02129.

³ Present address: Division of Radiation and Cancer Biology, New England Medical Center, Box 824, 750 Washington Street, Boston, MA 02111.

Received 2/21/91. Accepted 4/ 4/91.

This article has been cited by other articles:

				P. J. Durda, I. S. Dunn, L. B. Rose, D. Butera, E. M. Benson, F. Pandolfi, and J. T. Kurnick Induction of "Antigen Silencing" in Melanomas by Oncostatin M: Down-Modulation of Melanocyte Antigen Expression Mol. Cancer Res., April 1, 2003; 1(6): 411 - 419. [Abstract] [Full Text] [PDF]

				L. K. E. Rodrigues, B. J. Klencke, K. Vin-Christian, T. G. Berger, R. I. Crawford, J. R. Miller III, C. M. M. Ferreira, M. Nosrati, and M. Kashani-Sabet Altered Clinical Course of Malignant Melanoma in HIV-Positive Patients Arch Dermatol, June 1, 2002; 138(6): 765 - 770. [Abstract] [Full Text] [PDF]

				J. T. Kurnick, T. Ramirez-Montagut, L. A. Boyle, D. M. Andrews, F. Pandolfi, P. J. Durda, D. Butera, I. S. Dunn, E. M. Benson, S. J. P. Gobin, et al. A Novel Autocrine Pathway of Tumor Escape from Immune Recognition: Melanoma Cell Lines Produce a Soluble Protein That Diminishes Expression of the Gene Encoding the Melanocyte Lineage Melan-A/MART-1 Antigen Through Down-Modulation of Its Promoter J. Immunol., August 1, 2001; 167(3): 1204 - 1211. [Abstract] [Full Text] [PDF]

				M. C. Panelli, A. Riker, U. Kammula, E. Wang, K.-H. Lee, S. A. Rosenberg, and F. M. Marincola Expansion of Tumor-T Cell Pairs from Fine Needle Aspirates of Melanoma Metastases J. Immunol., January 1, 2000; 164(1): 495 - 504. [Abstract] [Full Text] [PDF]

				R. E. Sobol, D. L. Shawler, C. Carson, C. Van Beveren, D. Mercola, H. Fakhrai, M. A. Garrett, R. Barone, P. Goldfarb, R. M. Bartholomew, et al. Interleukin 2 Gene Therapy of Colorectal Carcinoma with Autologous Irradiated Tumor Cells and GeneticallyEngineered Fibroblasts: A Phase I Study Clin. Cancer Res., September 1, 1999; 5(9): 2359 - 2365. [Abstract] [Full Text] [PDF]

				K.-H. Lee, M. C. Panelli, C. J. Kim, A. I. Riker, M. P. Bettinotti, M. M. Roden, P. Fetsch, A. Abati, S. A. Rosenberg, and F. M. Marincola Functional Dissociation Between Local and Systemic Immune Response During Anti-Melanoma Peptide Vaccination J. Immunol., October 15, 1998; 161(8): 4183 - 4194. [Abstract] [Full Text] [PDF]

				M. Hishii, D. Andrews, L. A. Boyle, J. T. Wong, F. Pandolfi, P. J. van den Elsen, and J. T. Kurnick In vivo accumulation of the same anti-melanoma T cell clone in two different metastatic sites PNAS, February 18, 1997; 94(4): 1378 - 1383. [Abstract] [Full Text] [PDF]