Abstract
Oligoclonality was investigated in interleukin-2 (IL-2)-activated T cells (tumor-inrdtrating lymphocytes, TILs) residing in metastatic melanomas using seven different monoclonal antibodies (mAbs) specific for T-cell receptor (TCR) Vα or Vβ regions and flow cytometry. IL-2-activated TILs from 25 of 42 metastatic melanomas (60%) displayed oligoclonal expansion, whereas IL-2-activated peripheral bIIod mononuclear cells (PBMCs) from only 2 of 20 patients (10%) did so during 2–5 weeks in culture. Skin-derived lymphocytes from 20 patients were cultured; only four samples proliferated and none showed oligoclonal expansion. Preferential oligoclonal expansion of TILs was observed in Vβ8+ cells (10/42, P < 0.05), Vβ6.7+ cells (7/42, P < 0.05), and Vα2+ cells (7/42, not significant). Oligoclonal expansion of Vβ8+ cells was primarily found in T cells from subcutaneous metastases (8/20 cases, P < 0.05), whereas that of Vβ6.7+ cells and Vα2+ cells was also found in T cells from lymph node or organ metastases. These mAbs to TCR V regions stimulated effector TILs to produce interferon-γ, but not IL-2 or IL-4. Subcutaneous tumor-specific (Vβ8+ cells) and non-specific (Vβ6.7+ cells and Vα2+ cells) oligoclonalities were observed in IL-2-activated melanoma TILs, suggesting different immune responses among different sites of metastases.
Similar content being viewed by others
References
Moller DR, Konishi K, Kirby M, Balbi B and Crystal RG, 1988, Bias toward use of a specific T cell receptor β-chain variable region in a subgroup of individuals with sarcoidosis. Journal of Clinical Investigation, 82, 1183–1191.
Stamenkovic I, Stegagno M, Wright KA, Krane SM, Amento EP, Colvin RB, Duquesnoy RV and Kurnick JT, 1988, Clonal dominance among T-lympho cyte infiltrate in arthritis. Proceedings of the National Academy of Sciences, U.S.A., 85, 1179–1183.
Belldegrun A, Kasid A, Uppenkamp M, Topalian SL and Rosenberg SA, 1989, Human tumor-infiltrating lymphocytes. Analysis of lymphokine mRNA expression and relevance to cancer immunotherapy. Journal of Immunology, 142, 4520–4526.
Fishleder A, Finke JH, Tubbs R and Bukowski RM, 1990, Induction by interleukin 2 of oligoclonal expansion of cultured tumor-infiltrating lymphocytes. Journal of National Cancer Institute, 82, 124–128.
Nitta T, Oksenberg JR, Rao NA and Steinman L, 1990, Predominant expression of T cell receptor Vα7 in tumor-infiltrating lymphocytes of uveal melanoma. Science, 249, 672–674.
Yoshino I, Yano T, Yoshikai Y, Murata M, Sugimachi K, Kimura G and Nomoto K, 1991, Oligoclonal T lymphocytes infiltrating human lung cancer tissues. International Journal of Cancer, 47, 654–658.
Foon KA, 1989, Biological response modifiers: the new immunotherapy. Cancer Research, 49, 1621–1639.
Itoh K, Platsoucas CD and Balch CM, 1988, Autologous tumor-specific cytotoxic T lymphocytes in the infiltrate of human metastatic melanomas: activation by interleukin 2 and autologous tumor cells, and involvement of the T cell receptor. Journal of Experimental Medicine, 168, 1419–1441.
Choi Y, Lafferty JA, Clements JR, Todd JK, Gelfand EW, Kappler J, Marrack P and Kotzin BL, 1990, Selective expansion of T cells expressing Vβ2 in toxic shock syndrome. Journal of Experimental Medicine, 172, 981–984.
Balch CM and Milton GW, 1985, Treatment for advanced metastatic melanoma. Cutaneous Melanoma, edited by C. M. Balh and G. W. Milton (Philadelphia: J. B. Lippincott), pp. 251–273.
Itoh K, Tilden AB and Balch CM, 1986, Interleukin-2 activation of cytotoxic T lymphocytes infiltrating metastatic melanomas. Cancer Research, 45, 3011–3015.
Kimura N, Toyonaga B, Yoshikai Y, Du RP and Mak TW, 1987, Sequences and repertoire of the human T cell receptor α and β chain variable region genes in thymocytes. European Journal of Immunology, 17, 375–383.
Yoshikai Y, Kimura N, Toyonaga B and Mak TW, 1986, Sequences and repertoire of human T cell receptor α chain variable region genes in mature T lymphocytes. Journal of Experimental Medicine, 164, 90–103.
Sanders ME, Makgoba MW, Sharrow SO, Stephany D, Springer TA, Young HA and Shaw S, 1988, Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-γ production. Journal of Immunology, 140, 1401–1407.
Cardi G, Mastrangelo MJ and Berd D, 1989, Depletion of T cells with CD4+CD45R+ phenotype in lymphocytes that infiltrate subcutaneous metastases of human melanoma. Cancer Research, 49, 6562–6565.
Kappler J, Kotzin B, Herron L, Gelfand EW, Bigler RD, Boylston A, Carrel S, Posnett DN, Choi Y and Marrack P, 1989, Vβ-specific stimulation of human T cells by staphylococcal toxins. Science, 244, 811–813.
Fidler IJ, 1990, Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. clowes memorial award lecture. Cancer Research, 50, 6130–6138.
Governman J, Minard K, Shastri N, Hunkapiller T, Hansburg D, Secrarz E and Hood L, 1985, Rearranged β T cell receptor genes in a T helper T cell clone specific for lysozyme: no correlation between Vβ and MHC restriction. Cell, 40, 859–867.
Fink PJ, Matis LA, McElligott DL, Bookman M and Hedrick SM, 1986, Correlation between T-cell specificity and the structure of the antigen receptor. Nature, 321, 219–226.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Morita, T., Salmeron, M.A., Moser, R.P. et al. Oligoclonal expansion of Vβ8+ cells in interleukin-2-activated T cells residing in subcutaneous metastatic melanoma. Clin Exp Metast 10, 69–76 (1992). https://doi.org/10.1007/BF00163578
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00163578