Human Accessory Cells Activate Fresh, Normal, Tumor–Distant T Lymphocytes But Not Tumor–Infiltrating T Lymphocytes to Lyse Autologous Tumor Cells in a Primary Cytotoxic T Lymphocyte Assay in Renal Cell Carcinoma

2001 ◽  
Vol 40 (4) ◽  
pp. 427-433 ◽  
Author(s):  
Gero Kramer ◽  
Georg E. Steiner ◽  
Sabine Paiha ◽  
Alessandra Handisurya ◽  
Bob Djavan ◽  
...  
1987 ◽  
Vol 137 (4) ◽  
pp. 641-647 ◽  
Author(s):  
Etsuji Nakano ◽  
Yasuharu Tada ◽  
Yasuji Ichikawa ◽  
Hideki Fujioka ◽  
Minoru Matsuda ◽  
...  

1988 ◽  
Vol 168 (4) ◽  
pp. 1419-1441 ◽  
Author(s):  
K Itoh ◽  
C D Platsoucas ◽  
C M Balch

TIL from metastatic melanoma proliferated by greater than 1,000-fold (840-3,675, mean 1,543) after 6 wk in culture of mixtures of TIL and tumor cells with rIL-2 alone. Cytolysis was restricted to autologous tumor cells. CD8+ T cells were the predominant population of TIL before and after expansion, and were primarily responsible for autologous tumor-specific CTL activity. No other rIL-2-activated lymphocytes from peripheral blood, lymph nodes with melanoma metastasis, or TIL from sarcoma or renal cell carcinoma had autologous tumor-specific CTL activity. There were few or no CD16+ NK cells in TIL from metastatic melanoma before or after incubation with rIL-2, respectively. However, TIL from sarcoma or renal cell carcinoma contained a substantial proportion of CD3-CD16+ NK cells, which increased in number in culture with rIL-2. Purified CD16+ NK cells as well as CD3+CD16- T cells from rIL-2-activated TIL of renal cell carcinoma displayed MHC-nonrestricted cytotoxicity. At the clonal level as determined by limiting dilution, 8 of 10 clones from melanoma TIL displayed cytotoxicity restricted to autologous tumor cells, while all 13 clones from renal cancer TIL equally lysed autologous and allogeneic tumor cells. Anti-T cell receptor (TCR)-alpha/beta(WT31) mAb as well as anti-CD3 mAb inhibited autologous melanoma cell-specific CTL activity mediated by rIL-2-activated TIL at the effector phase. These two mAbs also inhibited rIL-2-dependent proliferation of these TIL when added to the culture. Pretreatment of fresh melanoma cells with mAb to MHC antigens followed by washing inhibited specific CTL activity. These results suggest that both TCR-alpha/beta on effector TIL and MHC antigens on fresh tumor cells are involved in the specific immune-recognition. After reaching maximum propagation, TIL from metastatic melanoma responded poorly to rIL-2 alone. However, stimulation with fresh autologous melanoma cells restored both CTL activity and proliferation in response to rIL-2. The latter is associated with IL-2 receptor (Tac antigen) expression on the surface. These results indicate that TIL from metastatic melanomas may have unique characteristics different from lymphocytes obtained from the other sources, and may contain precursor CTL sensitized in vivo to autologous tumor cells, and thus can be propagated in larger numbers with rIL-2 alone while retaining autologous tumor-specific CTL activity.


1996 ◽  
Vol 183 (6) ◽  
pp. 2501-2508 ◽  
Author(s):  
D Brändle ◽  
F Brasseur ◽  
P Weynants ◽  
T Boon ◽  
B Van den Eynde

Many human tumor cells have been shown to express antigens that are recognized by autologous cytotoxic T lymphocytes (CTL) and the molecular nature of a number of melanoma antigens has been defined recently. Here we describe the characterization of an antigen recognized on a renal cell carcinoma by autologous CTL clones. This antigen is encoded by the HLA-A2 gene present in the tumor cells. The sequence of this gene differs from the HLA-A2 sequence found in autologous peripheral blood lymphocytes by a point mutation that results in an arginine to isoleucine exchange at residue 170, which is located on the alpha-helix of the alpha 2 domain. Transfection experiments with the normal and mutated HLA-A2 cDNA demonstrated that this amino acid replacement was responsible for the recognition of the HLA-A2 molecule expressed on the tumor cells. The mutant HLA-A2 gene was also detected in the original tumor tissue from the patient, excluding the possibility that the mutation had appeared in vitro. Thus, HLA class I molecules carrying a tumor-specific mutation can be involved in the recognition of tumor cells by autologous CTL.


2021 ◽  
Vol 206 (Supplement 3) ◽  
Author(s):  
Soki Kashima ◽  
Takuya Maeda ◽  
Kyoko Masuda ◽  
Seiji Nagano ◽  
Takamitsu Inoue ◽  
...  

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