Skewed distribution of TCR Vα 7-bearing T cells within tumor-infiltrating lymphocytes of HLA-A24(9)-positive patients with malignant glioma

Abstract

The identification and propagation of T cells with anti-tumor reactivity is critical for understanding the human immune response to tumors, which may possibly be useful in the successful implementation of adoptive immunotherapy against cancer. In order to address this question, we examined the diversity of mRNA transcripts of T-cell receptor (TCR) Vα and Vβ genes in tumor-infiltrating lymphocytes (TIL) of 12 glioma specimens obtained at surgery. Using the polymerase chain reaction (PCR) method and primers for 18 different human TCR Vα and 22 Vβ families to analyze TCR V-(D)-J-C gene rearrangements, we detected a limited expression of TCR variable region, Vα genes and predominant usage of Vα 7 within glioma TIL. TCR Vβ gene usage was more diverse than that for Vα, but TCR Vβ 13.1 was dominantly expressed in 9 out of 12 patients. In addition, we analyzed the percentage of each Vα- and Vβ-bearing T-cell subpopulation in TIL as well as in peripheral blood lymphocytes (PBL) quantitatively. The distribution of T-cell subpopulation bearing each Vα or Vβ subfamily was variable and uneven in all cases. In 3 cases, the distribution of Vα 7-bearing T cells in TIL was far higher than in PBL. This phenomenon was not found in T cells bearing TCR Vβ 13.1. We also performed human leukocyte antigen (HLA) typing in these patients, and A24(9) was observed in 8 out of 11 patients. Among them all 3 patients who showed a skewed distribution of Vα 7-bearing T cells in TIL expressed HLA-A24(9). There was no correlation between particular class I or II type and TCR Vβ gene usage. From these results, it was strongly suggested that T cells bearing TCR Vα 7 might be targeted to antigenic determinants on glioma cells, and such T-cell population may be useful as effector cells for cancer immunotherapy.