Dacarbazine treatment before peptide vaccination enlarges T-cell repertoire diversity of Melan-A-specific, tumor-reactive CTL in melanoma patients

Belinda Palermo, Duilia Del Bello, Alessandra Sottini, Federico Serana, Claudia Ghidini, Novella Gualtieri, Virginia Ferraresi, Caterina Catricalà, Filippo Belardelli, Enrico Proietti, Pier Giorgio Natali, Luisa Imberti, Paola Nisticò

Research output: Contribution to journalArticle

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 effectormemory 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.

Original languageEnglish
Pages (from-to)7084-7092
Number of pages9
JournalCancer Research
Volume70
Issue number18
DOIs
Publication statusPublished - Sep 15 2010

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Dacarbazine treatment before peptide vaccination enlarges T-cell repertoire diversity of Melan-A-specific, tumor-reactive CTL in melanoma patients'. Together they form a unique fingerprint.

  • Cite this

    Palermo, B., Del Bello, D., Sottini, A., Serana, F., Ghidini, C., Gualtieri, N., Ferraresi, V., Catricalà, C., Belardelli, F., Proietti, E., Natali, P. G., Imberti, L., & Nisticò, P. (2010). Dacarbazine treatment before peptide vaccination enlarges T-cell repertoire diversity of Melan-A-specific, tumor-reactive CTL in melanoma patients. Cancer Research, 70(18), 7084-7092. https://doi.org/10.1158/0008-5472.CAN-10-1326