T‐cell receptor Vβ gene usage by T cells reactive with the tumor‐rejection antigen SART‐1 in oral squamous cell carcinoma

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Abstract
We recently described that the SART‐1690–698 peptide could induce HLA‐A24‐restricted cytotoxic T lymphocytes (CTLs), which recognize the SART‐1 tumor cells from peripheral blood mononuclear cells (PBMCs) of HLA‐A24+ cancer patients. In our study, in 5 of 14 HLA‐A24+ patients with oral squamous cell carcinomas (SCCs), CTLs could be induced with the SART‐1690–698 peptide from the PBMCs. In 2 of the patients from whom the highest CTL activities were induced, the T‐cell receptor (TCR) Vβ repertoire expressed by the SART‐1690–698‐specific CTLs was found to be restricted and multiple Vβ families were predominantly expressed in each patient. Although the predominant Vβ families were different between the 2 patients, Vβ7 was highly and commonly predominant. The same predominant Vβ families were also detected in the tumor‐infiltrating lymphocytes (TILs) from each patient, and each Vβ family contained one or more unique T‐cell clonotypes. The unique T‐cell clonotypes were found to be common between the TILs and SART‐1690–698‐specific CTLs from each patient, and especially 2 T‐cell clonotypes with Vβ7 were identical even in the 2 patients. One of the 2 T‐cell clonotypes with Vβ7 was detected in the TILs from 11 of 14 HLA‐A24+ patients and another was found in those from 8 of HLA‐A24+ patients, while none of 10 HLA‐A24− patients demonstrated both T‐cell clonotypes. These results strongly suggest that the T‐cell clonotypes with Vβ7 are major TCR Vβ genes expressed by SART‐1690–698‐specific CTLs. Furthermore, autologous tumor cells from one of the HLA‐A24+ patients stimulated the PBMCs and regional lymph node cells (LNCs) to expand the same T‐cell clonotypes as those in the SART‐1690–698‐specific CTLs. These results strongly suggest that the SART‐1690–698‐specific CTLs clearly accumulate in vivo, especially in the TILs, as a consequence of in situ antigenic stimulation by autologous tumor cells. The identification of the unique TCR Vβ genes used by SART‐1259‐specific CTLs should help to improve the diagnosis of the specific immune response in patients with SART‐1 cancers, especially during anticancer immunotherapy.