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 language | English |
|---|---|
| Pages (from-to) | 1065-1076 |
| Number of pages | 12 |
| Journal | Cancer Immunology, Immunotherapy |
| Volume | 56 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 2007 |
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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 journal › Article
}
TY - JOUR
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
PY - 2007/7
Y1 - 2007/7
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
UR - http://www.scopus.com/inward/record.url?scp=34247587786&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34247587786&partnerID=8YFLogxK
U2 - 10.1007/s00262-006-0268-x
DO - 10.1007/s00262-006-0268-x
M3 - Article
C2 - 17195078
AN - SCOPUS:34247587786
VL - 56
SP - 1065
EP - 1076
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
SN - 0340-7004
IS - 7
ER -