Short-term kinetics of tumor antigen expression in response to vaccination

The melanoma patient's immune response to tumor has been extensively studie d. Yet, the frequently observed coexistence of tumor-associated Ag (TAA)-sp ecific T cells with their target cells in vivo remains unexplained. Loss of TAA expression might contribute to this paradox. We studied TAA expression in metastases by obtaining fine-needle aspirations from 52 tumor lesions i n 30 patients with melanoma before and soon after immunotherapy. Limitation s due to low amounts of starting material were overcome with a high fidelit y antisense RNA amplification method. TAA expression was measured by quanti tative real-time PCR of anti-sense RNA. Decrease in gp100/Pmel-17 TAA prece ded tumor disappearance in several instances and could be best explained by immune selection because most patients had received gp100/Pmel-17-specific vaccination. Conversely, immune selection was absent in nonregressing lesi ons. These observations suggest that vaccination, when successful, triggers a broad inflammatory reaction that can lead to tumor destruction despite i mmune selection. Additionally, lack of clinical response might be attribute d to lack of this initiating event rather than immune escape. This study pr ovides an insight into the natural history of tumors and defines a strategy for the characterization of gene expression in tumors during therapy.