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

Wataru Kumamaru, Seiji Nakamura, Tsutomu Kadena, Akira Yamada, Eiji Kawamura, Masanori Sasaki, Yukiko Ohyama, Takeshi Toyoshima, Jun Nosuke Hayashida, Kyogo Itoh, Kanemitsu Shirasuna

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

We recently described that the SART-1690-698 peptide could induce HLA-A24-restricted cytotoxic T lymphocytes (CTLs), which recognize the SART-1259+ 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-1 690-698-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-1259+ cancers, especially during anticancer immunotherapy.

Original languageEnglish
Pages (from-to)686-695
Number of pages10
JournalInternational Journal of Cancer
Volume108
Issue number5
DOIs
Publication statusPublished - Feb 20 2004

Fingerprint

T-Cell Receptor Genes
Neoplasm Antigens
HLA-A24 Antigen
Squamous Cell Carcinoma
Cytotoxic T-Lymphocytes
T-Lymphocytes
Tumor-Infiltrating Lymphocytes
Blood Cells
Neoplasms
Rejection (Psychology)
Peptides
T-Cell Antigen Receptor
Immunotherapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

T-cell receptor Vβ gene usage by T cells reactive with the tumor-rejection antigen SART-1 in oral squamous cell carcinoma. / Kumamaru, Wataru; Nakamura, Seiji; Kadena, Tsutomu; Yamada, Akira; Kawamura, Eiji; Sasaki, Masanori; Ohyama, Yukiko; Toyoshima, Takeshi; Hayashida, Jun Nosuke; Itoh, Kyogo; Shirasuna, Kanemitsu.

In: International Journal of Cancer, Vol. 108, No. 5, 20.02.2004, p. 686-695.

Research output: Contribution to journalArticle

Kumamaru, Wataru ; Nakamura, Seiji ; Kadena, Tsutomu ; Yamada, Akira ; Kawamura, Eiji ; Sasaki, Masanori ; Ohyama, Yukiko ; Toyoshima, Takeshi ; Hayashida, Jun Nosuke ; Itoh, Kyogo ; Shirasuna, Kanemitsu. / T-cell receptor Vβ gene usage by T cells reactive with the tumor-rejection antigen SART-1 in oral squamous cell carcinoma. In: International Journal of Cancer. 2004 ; Vol. 108, No. 5. pp. 686-695.
@article{041a2a2303c9476fbc3d57e8c1ab8506,
title = "T-cell receptor Vβ gene usage by T cells reactive with the tumor-rejection antigen SART-1 in oral squamous cell carcinoma",
abstract = "We recently described that the SART-1690-698 peptide could induce HLA-A24-restricted cytotoxic T lymphocytes (CTLs), which recognize the SART-1259+ 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-1 690-698-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-1259+ cancers, especially during anticancer immunotherapy.",
author = "Wataru Kumamaru and Seiji Nakamura and Tsutomu Kadena and Akira Yamada and Eiji Kawamura and Masanori Sasaki and Yukiko Ohyama and Takeshi Toyoshima and Hayashida, {Jun Nosuke} and Kyogo Itoh and Kanemitsu Shirasuna",
year = "2004",
month = "2",
day = "20",
doi = "10.1002/ijc.11591",
language = "English",
volume = "108",
pages = "686--695",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - T-cell receptor Vβ gene usage by T cells reactive with the tumor-rejection antigen SART-1 in oral squamous cell carcinoma

AU - Kumamaru, Wataru

AU - Nakamura, Seiji

AU - Kadena, Tsutomu

AU - Yamada, Akira

AU - Kawamura, Eiji

AU - Sasaki, Masanori

AU - Ohyama, Yukiko

AU - Toyoshima, Takeshi

AU - Hayashida, Jun Nosuke

AU - Itoh, Kyogo

AU - Shirasuna, Kanemitsu

PY - 2004/2/20

Y1 - 2004/2/20

N2 - We recently described that the SART-1690-698 peptide could induce HLA-A24-restricted cytotoxic T lymphocytes (CTLs), which recognize the SART-1259+ 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-1 690-698-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-1259+ cancers, especially during anticancer immunotherapy.

AB - We recently described that the SART-1690-698 peptide could induce HLA-A24-restricted cytotoxic T lymphocytes (CTLs), which recognize the SART-1259+ 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-1 690-698-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-1259+ cancers, especially during anticancer immunotherapy.

UR - http://www.scopus.com/inward/record.url?scp=9144267770&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9144267770&partnerID=8YFLogxK

U2 - 10.1002/ijc.11591

DO - 10.1002/ijc.11591

M3 - Article

C2 - 14696095

AN - SCOPUS:9144267770

VL - 108

SP - 686

EP - 695

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 5

ER -