Abstract：
:Combination of chemotherapy and immunotherapy to increase the effectiveness of an antitumor immune response is currently regarded as an attractive antitumor strategy. In a pilot clinical trial, we have recently documented an increase of melanoma antigen A (Melan-A)-specific, tumor-reactive, long-lasting effector-memory CD8(+) T cells after the administration of dacarbazine (DTIC) 1 day before peptide vaccination in melanoma patients. Global transcriptional analysis revealed a DTIC-induced activation of genes involved in the immune response and leukocyte activation. To identify the possible mechanisms underlying this improved immune response, we have compared the endogenous and the treatment-induced anti-Melan-A response at the clonal level in patients treated with the vaccine alone or with DTIC plus vaccine. We report a progressive widening of T-cell receptor (TCR) repertoire diversity, accompanied by high avidity and tumor reactivity, only in Melan-A-specific T-cell clones of patients treated with chemoimmunotherapy, with a trend toward longer survival. Differently, patients treated with vaccine alone showed a tendency to narrowing the TCR repertoire diversity, accompanied by a decrease of tumor lytic activity in one patient. Collectively, our findings indicate that DTIC plus vaccination shapes the TCR repertoire in terms of diversity and antitumor response, suggesting that this combined therapy could be effective in preventing melanoma relapse.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Palermo B,Del Bello D,Sottini A,Serana F,Ghidini C,Gualtieri N,Ferraresi V,Catricalà C,Belardelli F,Proietti E,Natali PG,Imberti L,Nisticò Pdoi
10.1158/0008-5472.CAN-10-1326subject
Has Abstractpub_date
2010-09-15 00:00:00pages
7084-92issue
18eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-10-1326journal_volume
70pub_type
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