CD8+ T lymphocytes isolated from renal cancer patients recognize tumour cells through an HLA- and TCR/CD3-independent pathway

Ilaria Lionello, Patrizia Mangia, Luca Gattinoni, Daniela Pende, Arcadi Cippone, Marialuisa Sensi, Patrizio Rigatti, Catia Traversari

Research output: Contribution to journalArticle

Abstract

Purpose: The aim of this study was to characterize the immune response of patients affected by renal cell carcinoma (RCC). Methods: Long-term RCC lines were established by retroviral-mediated transfer of the large T-antigen of SV40 into fresh carcinoma cells. Reactive T cell effectors were generated by iterative stimulations of patients' PBMC with autologous tumour cells. Results: This protocol led to the induction of CD8+ T cell clones reactive against the autologous tumour, but not against NK-sensitive cell lines. However, some of these effectors recognize normal renal cells, allogeneic renal carcinoma cell lines and colon and non-small cell lung carcinomas but not melanomas and lymphoblastoid lines, without evidence of shared classical HLA class I (HLA-I) molecules. Further characterization performed on the CD8 + TCR α/β+ clone, CTL30, demonstrated that neither expression of CD1, HLA-Ia nor HLA-Ib, correlated with the T cells' recognition. Moreover, β2m expression by target cells was not required to achieve interaction of tumour-effector cells. In agreement with this observation, the lytic activity of CTL30 was not inhibited by anti-HLA-I Ab, and antigen expression was not affected by inhibitors of antigen processing. Lytic activity of CTL30, while partially inhibited by anti-NKG2D, could not be abolished by anti-CD3 Abs. Moreover, growth and expansion of CTL30 was sustained only by T cell interaction with antigen-expressing tumour cells; unspecific mitogenic stimuli, such as anti-CD3 and PHA, did not allow T cell expansion. These results demonstrated the existence of an α/β T cell population, recognizing epithelial tumour cells through an HLA-unrestricted, CD3-independent mechanism.

Original languageEnglish
Pages (from-to)1065-1076
Number of pages12
JournalCancer Immunology, Immunotherapy
Volume56
Issue number7
DOIs
Publication statusPublished - Jul 2007

Fingerprint

Kidney Neoplasms
T-Lymphocytes
Renal Cell Carcinoma
Neoplasms
Cell Line
Clone Cells
Histocompatibility Antigens Class I
Viral Tumor Antigens
Antigen Presentation
Neoplasm Antigens
Non-Small Cell Lung Carcinoma
Cell Communication
Natural Killer Cells
Melanoma
Colon
Epithelial Cells
Carcinoma
Kidney
Growth
Population

Keywords

  • HLA restriction
  • Renal cancer
  • T cells
  • Tumour immunity

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

Cite this

CD8+ T lymphocytes isolated from renal cancer patients recognize tumour cells through an HLA- and TCR/CD3-independent pathway. / Lionello, Ilaria; Mangia, Patrizia; Gattinoni, Luca; Pende, Daniela; Cippone, Arcadi; Sensi, Marialuisa; Rigatti, Patrizio; Traversari, Catia.

In: Cancer Immunology, Immunotherapy, Vol. 56, No. 7, 07.2007, p. 1065-1076.

Research output: Contribution to journalArticle

Lionello, Ilaria ; Mangia, Patrizia ; Gattinoni, Luca ; Pende, Daniela ; Cippone, Arcadi ; Sensi, Marialuisa ; Rigatti, Patrizio ; Traversari, Catia. / CD8+ T lymphocytes isolated from renal cancer patients recognize tumour cells through an HLA- and TCR/CD3-independent pathway. In: Cancer Immunology, Immunotherapy. 2007 ; Vol. 56, No. 7. pp. 1065-1076.
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T1 - CD8+ T lymphocytes isolated from renal cancer patients recognize tumour cells through an HLA- and TCR/CD3-independent pathway

AU - Lionello, Ilaria

AU - Mangia, Patrizia

AU - Gattinoni, Luca

AU - Pende, Daniela

AU - Cippone, Arcadi

AU - Sensi, Marialuisa

AU - Rigatti, Patrizio

AU - Traversari, Catia

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N2 - Purpose: The aim of this study was to characterize the immune response of patients affected by renal cell carcinoma (RCC). Methods: Long-term RCC lines were established by retroviral-mediated transfer of the large T-antigen of SV40 into fresh carcinoma cells. Reactive T cell effectors were generated by iterative stimulations of patients' PBMC with autologous tumour cells. Results: This protocol led to the induction of CD8+ T cell clones reactive against the autologous tumour, but not against NK-sensitive cell lines. However, some of these effectors recognize normal renal cells, allogeneic renal carcinoma cell lines and colon and non-small cell lung carcinomas but not melanomas and lymphoblastoid lines, without evidence of shared classical HLA class I (HLA-I) molecules. Further characterization performed on the CD8 + TCR α/β+ clone, CTL30, demonstrated that neither expression of CD1, HLA-Ia nor HLA-Ib, correlated with the T cells' recognition. Moreover, β2m expression by target cells was not required to achieve interaction of tumour-effector cells. In agreement with this observation, the lytic activity of CTL30 was not inhibited by anti-HLA-I Ab, and antigen expression was not affected by inhibitors of antigen processing. Lytic activity of CTL30, while partially inhibited by anti-NKG2D, could not be abolished by anti-CD3 Abs. Moreover, growth and expansion of CTL30 was sustained only by T cell interaction with antigen-expressing tumour cells; unspecific mitogenic stimuli, such as anti-CD3 and PHA, did not allow T cell expansion. These results demonstrated the existence of an α/β T cell population, recognizing epithelial tumour cells through an HLA-unrestricted, CD3-independent mechanism.

AB - Purpose: The aim of this study was to characterize the immune response of patients affected by renal cell carcinoma (RCC). Methods: Long-term RCC lines were established by retroviral-mediated transfer of the large T-antigen of SV40 into fresh carcinoma cells. Reactive T cell effectors were generated by iterative stimulations of patients' PBMC with autologous tumour cells. Results: This protocol led to the induction of CD8+ T cell clones reactive against the autologous tumour, but not against NK-sensitive cell lines. However, some of these effectors recognize normal renal cells, allogeneic renal carcinoma cell lines and colon and non-small cell lung carcinomas but not melanomas and lymphoblastoid lines, without evidence of shared classical HLA class I (HLA-I) molecules. Further characterization performed on the CD8 + TCR α/β+ clone, CTL30, demonstrated that neither expression of CD1, HLA-Ia nor HLA-Ib, correlated with the T cells' recognition. Moreover, β2m expression by target cells was not required to achieve interaction of tumour-effector cells. In agreement with this observation, the lytic activity of CTL30 was not inhibited by anti-HLA-I Ab, and antigen expression was not affected by inhibitors of antigen processing. Lytic activity of CTL30, while partially inhibited by anti-NKG2D, could not be abolished by anti-CD3 Abs. Moreover, growth and expansion of CTL30 was sustained only by T cell interaction with antigen-expressing tumour cells; unspecific mitogenic stimuli, such as anti-CD3 and PHA, did not allow T cell expansion. These results demonstrated the existence of an α/β T cell population, recognizing epithelial tumour cells through an HLA-unrestricted, CD3-independent mechanism.

KW - HLA restriction

KW - Renal cancer

KW - T cells

KW - Tumour immunity

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