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Abstract
The use of HLA class I tetramers has provided important insights into the analysis of tumor-specific immune responses, and allowed direct demonstration of expanded populations of activated tumor-specific cytotoxic T lymphocytes (CTLs) in some patients with metastatic melanoma. Our previous studies have established that the largest excess of tumor-specific CTLs is observed in tumor infiltrated lymph nodes. Our results indicate that in vivo priming of tumor-specific CTLs is a late phenomenon, since only stage III and IV patients have an active immune response, while stage I -II patients have either undetectable or, in the case of melan-A26-35 specific responses, tumor-specific CTLs with functional and phenotypic markers of naive population. If many patients are failing to prime and activate their tumor-specific CTLs at earlier stages of their disease then immunogens capable of priming in vivo these cells may be clinically helpful, as they will be able to recruit rapidly a large number of tumor-specific CTLs. The main challenge for tumor immunotherapy is to jumpstart the immune response at a far earlier stage of disease to maximize the possibility for clinical impact.
The main focus of my talk will be: 1) the analysis of the immunodominance of pox-viral specific CTLs in melanoma patients receiving recombinant modified vaccinia Ankara and 2) the interplay between innate and adaptive immune system to elicit strong tumor-specific CD4+ and CD8+ T-cell responses.
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