title: CD8(+) T lymphocytes isolated from renal cancer patients recognize tumour cells through an HLA- and TCR/CD3-independent pathway.
abstract: OBJECTIVE
  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 alpha/beta(+) clone, CTL30, demonstrated that neither expression of CD1, HLA-Ia nor HLA-Ib, correlated with the T cells' recognition. Moreover, beta2m 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 alpha/beta T cell population, recognizing epithelial tumour cells through an HLA-unrestricted, CD3-independent mechanism.
authors.affiliation: Cancer Immunotherapy and Gene Therapy Program, Scientific Institute H. San Raffaele, Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lionello
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mangia
authors.forename: Luca
authors.initials: L
authors.lastname: Gattinoni
authors.forename: Daniela
authors.initials: D
authors.lastname: Pende
authors.forename: Arcadi
authors.initials: A
authors.lastname: Cippone
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Sensi
authors.forename: Patrizio
authors.initials: P
authors.lastname: Rigatti
authors.forename: Catia
authors.initials: C
authors.lastname: Traversari
mesh_terms: D017252:CD3 Complex / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
chemical_list: D017252:CD3 Complex; D006680:HLA Antigens; D011948:Receptors, Antigen, T-Cell