Functional dissociation between local and systemic immune response during anti-melanoma peptide vaccination

Kang Hun Lee, Monica C. Panelli, Christina J. Kim, Adam I. Riker, Maria P. Bettinotti, Matthew M. Roden, Patricia Fetsch, Andrea Abati, Steven A. Rosenberg, Francesco M. Marincola

Research output: Contribution to journalArticle

Abstract

Peptide vaccination against tumor Ags can induce powerful systemic CTL responses. However, in the majority of patients, no tumor regression is noted. To study this discrepancy, we analyzed CTL reactivity in a melanoma patient (F001) vaccinated with g209-2M peptide, a single residue variant of gp100209-217. G209/g209-2M-reactive CTL were identified in post- but not prevaccination PBL. Limiting dilution analysis identified one predominant CTL clone (C1-35), with TCR Vβ6s2, recognizing g209/HLA-A*0201-expressing targets. Additionally, two autologous melanoma lines (F001TU-3 and -4) and 20 separate tumor-infiltrating lymphocyte cultures were generated from a fine needle aspirate of a metastatic lesion progressing after initial response to vaccination. Both F001TU did not express gp100 and were not recognized by C1- 35. Loss of gp100 by F001TU correlated with a marked reduction of gp100 expression in the same metastatic legion compared with prevaccination. Thus, ineffectiveness of C1-35 and tumor progression could be best explained by loss of target Ag expression. Interestingly, 12 of 20 tumor-infiltrating lymphocyte cultures recognized F001TU, but none demonstrated g209/g209-2M reactivity, suggesting a functional dissociation between systemic and local immune response. This study suggests that vaccination effects must be analyzed in the target tissue, rather than in the systemic circulation alone.

Original languageEnglish (US)
Pages (from-to)4183-4194
Number of pages12
JournalJournal of Immunology
Volume161
Issue number8
StatePublished - Oct 15 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Lee, K. H., Panelli, M. C., Kim, C. J., Riker, A. I., Bettinotti, M. P., Roden, M. M., Fetsch, P., Abati, A., Rosenberg, S. A., & Marincola, F. M. (1998). Functional dissociation between local and systemic immune response during anti-melanoma peptide vaccination. Journal of Immunology, 161(8), 4183-4194.