Zippelius, Alfred and Batard, Pascal and Rubio-Godoy, Verena and Bioley, Gilles and Lienard, Danielle and Lejeune, Ferdy and Rimoldi, Donata and Guillaume, Philippe and Meidenbauer, Norbert and Mackensen, Andreas and Rufer, Nathalie and Lubenow, Norbert and Speiser, Daniel and Cerottini, Jean-Charles and Romero, Pedro and Pittet, Mikael J. (2004) Effector function of human tumor-specific CD8 T cells in melanoma lesions: A state of local functional tolerance. CANCER RESEARCH, 64 (8). pp. 2865-2873. ISSN 0008-5472, 1538-7445
Full text not available from this repository. (Request a copy)Abstract
Although tumor-specific CD8 T-cell responses often develop in cancer patients, they rarely result in tumor eradication. We aimed at studying directly the functional efficacy of tumor-specific CD8 T cells at the site of immune attack. Tumor lesions in lymphoid and nonlymphoid tissues (metastatic lymph nodes and soft tissue/visceral metastases, respectively) were collected from stage III/IV melanoma patients and investigated for the presence and function of CD8 T cells specific for the tumor differentiation antigen Melan-A/MART-1. Comparative analysis was conducted with peripheral blood T cells. We provide evidence that in vivo-priming selects, within the available naive Melan-A/MART-1-specific CD8 T-cell repertoire, cells with high T-cell receptor avidity that can efficiently kill melanoma cells in vitro. In vivo, primed Melan-A/MART-1-specific CD8 T cells accumulate at high frequency in both lymphoid and nonlymphoid tumor lesions. Unexpectedly, however, whereas primed Melan-A/MART-1-specific CD8 T cells that circulate in the blood display robust inflammatory and cytotoxic functions, those that reside in tumor lesions (particularly in metastatic lymph nodes) are functionally tolerant. We show that both the lymph node and the tumor environments blunt T-cell effector functions and offer a rationale for the failure of tumor-specific responses to effectively counter tumor progression.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; IMMUNE-RESPONSE; REACTIVE CTL; ANTIGEN; PEPTIDE; DIFFERENTIATION; SELF; POPULATION; GENERATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Jul 2021 08:49 |
| Last Modified: | 21 Jul 2021 08:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/37747 |
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