Oligoclonal expansion of Vβ8⁺ cells in interleukin-2-activated T cells residing in subcutaneous metastatic melanoma

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.