Strategies and challenges in eliciting immunity to melanoma

Andrew R. Ferguson, Lisa A. Nichols, Angela L. Zarling, Elizabeth Thompson, C. Colin Brinkman, Kristian M. Hargadon, Timothy N. Bullock, Victor H. Engelhard

Research output: Contribution to journalReview article

Abstract

The ability of CD8+ T cells to recognize melanoma tumors has led to the development of immunotherapeutic approaches that use the antigens CD8+ T cells recognize. However, clinical response rates have been disappointing. Here we summarize our work to understand the mechanisms of self-tolerance that limit responses to currently utilized antigens and our approach to identify new antigens directly tied to malignancy. We also explore several aspects of the anti-tumor immune response induced by peptide-pulsed dendritic cells (DCs). DCs differentially augment the avidity of recall T cells specific for self-antigens and overcome a process of aberrant CD8+ T-cell differentiation that occurs in tumor-draining lymph nodes. DC migration is constrained by injection route, resulting in immune responses in localized lymphoid tissue, and differential control of tumors depending on their location in the body. We demonstrate that CD8+ T-cell differentiation in different lymphoid compartments alters the expression of homing receptor molecules and leads to the presence of systemic central memory cells. Our studies highlight several issues that must be addressed to improve the efficacy of tumor immunotherapy.

Original languageEnglish (US)
Pages (from-to)28-42
Number of pages15
JournalImmunological Reviews
Volume222
Issue number1
DOIs
StatePublished - Apr 2008
Externally publishedYes

Fingerprint

Immunity
Melanoma
T-Lymphocytes
Dendritic Cells
Neoplasms
Cell Differentiation
CD8 Antigens
Self Tolerance
Antigens
Autoantigens
Lymphoid Tissue
Immunotherapy
Cell Movement
Lymph Nodes
Peptides
Injections

Keywords

  • CD8 T cells
  • Melanoma
  • Memory
  • Phosphopeptides
  • Regional immunity
  • Tumor antigens

ASJC Scopus subject areas

  • Immunology

Cite this

Ferguson, A. R., Nichols, L. A., Zarling, A. L., Thompson, E., Brinkman, C. C., Hargadon, K. M., ... Engelhard, V. H. (2008). Strategies and challenges in eliciting immunity to melanoma. Immunological Reviews, 222(1), 28-42. https://doi.org/10.1111/j.1600-065X.2008.00620.x

Strategies and challenges in eliciting immunity to melanoma. / Ferguson, Andrew R.; Nichols, Lisa A.; Zarling, Angela L.; Thompson, Elizabeth; Brinkman, C. Colin; Hargadon, Kristian M.; Bullock, Timothy N.; Engelhard, Victor H.

In: Immunological Reviews, Vol. 222, No. 1, 04.2008, p. 28-42.

Research output: Contribution to journalReview article

Ferguson, AR, Nichols, LA, Zarling, AL, Thompson, E, Brinkman, CC, Hargadon, KM, Bullock, TN & Engelhard, VH 2008, 'Strategies and challenges in eliciting immunity to melanoma', Immunological Reviews, vol. 222, no. 1, pp. 28-42. https://doi.org/10.1111/j.1600-065X.2008.00620.x
Ferguson AR, Nichols LA, Zarling AL, Thompson E, Brinkman CC, Hargadon KM et al. Strategies and challenges in eliciting immunity to melanoma. Immunological Reviews. 2008 Apr;222(1):28-42. https://doi.org/10.1111/j.1600-065X.2008.00620.x
Ferguson, Andrew R. ; Nichols, Lisa A. ; Zarling, Angela L. ; Thompson, Elizabeth ; Brinkman, C. Colin ; Hargadon, Kristian M. ; Bullock, Timothy N. ; Engelhard, Victor H. / Strategies and challenges in eliciting immunity to melanoma. In: Immunological Reviews. 2008 ; Vol. 222, No. 1. pp. 28-42.
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