Human tumor-infiltrating lymphocytes

We review seven key areas in human tumor-infiltrating lymphocyte (TIL) research: yield, subpopulation phenotypes, interleukin 2 (IL-2)-induced proliferation, cytotoxicity, lymphokine production, oligoclonality, and T cell receptor (TCR) Vα and Vβ gene usage of tumor-specific T cells. Most cancers contain a significant infiltration of lymphocytes. T cells, in particular CD4⁺ T cells, were the predominant population. IL-2-induced TIL proliferation was greater than that of peripheral blood mononuclear cells (PBMCs). IL-2-activated TILs from some cancers (melanoma, bladder cancer, and glioma) displayed autologous tumor-specific cytotoxicity, whereas those from other cancers primarily had major histocompatibility complex (MHC)- nonrestricted cytotoxicity (renal cell carcinoma (RCC), head and neck cancer, and liver carcinoma). MHC-nonrestricted interferon-γ (IFN-γ) production was characteristic of IL-2-activated TILs in most cases of melanomas and RCCs. In contrast to PBMCs or lymphocytes from normal tissues, T cells from TILs of most melanomas and RCCs displayed oligoclonality following activation with IL-2. Usage of TCR Vα or Vβ gene for melanoma-specific cytotoxic T lymphocyte (CTL) clones that were derived from TIL was not restricted to one or several genes, but was rather diverse. In summary, TIL contains tumor- specific T cells and therefore will be an appropriate source for understanding the cellular and molecular basis of host-tumor interaction.