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The paradox of T-cell-mediated antitumor immunity in spite of poor clinical outcome in human melanoma.
- Source :
-
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2004 Oct; Vol. 53 (10), pp. 855-64. Date of Electronic Publication: 2004 Jun 03. - Publication Year :
- 2004
-
Abstract
- Human melanoma is hardly ever curable at an advanced stage, but overwhelming evidence from untreated or vaccinated patients indicates that this tumor is highly antigenic and frequently immunogenic. Here, we review recent results indicating that CD8(+) T cell-mediated antitumor immunity is activated at the systemic and tumor level in the early clinical stages (AJCC stages I and II) and continues to be promoted, in a fraction of patients, even in metastatic disease (stages III and IV). This evidence was obtained by looking at frequency, differentiation phenotype, and function of antitumor T cells in periphery and tumor site of melanoma patients. On the other hand, the paradox of immunity in spite of poor clinical evolution of the disease, points toward a model of concurrent evolution of immunity and tumor escape. As melanoma progresses to metastatic disease, powerful mechanisms of tumor evasion from immune recognition, and of immunosuppression, are activated, thus tilting the balance between immunity and escape in favor of tumor resistance to host defense. Nevertheless, recent developments in our understanding of regulation of T cell-mediated immunity can provide clues to the prospects for improved immunotherapy approaches. By integrating the information from basic research in immunology, from murine tumor models, and from trials of immunotherapy, we discuss how the most relevant steps of the antitumor response should be manipulated with greater efficacy by future clinical trials.
- Subjects :
- Antigens, Differentiation immunology
Antigens, Neoplasm immunology
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Cancer Vaccines therapeutic use
Cell Differentiation
Clinical Trials as Topic
Disease Progression
Humans
Lymphocytes, Tumor-Infiltrating immunology
Melanoma pathology
Melanoma therapy
Models, Immunological
Neoplasm Metastasis
Neoplasm Staging
Treatment Failure
Melanoma immunology
T-Lymphocyte Subsets immunology
Tumor Escape immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0340-7004
- Volume :
- 53
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cancer immunology, immunotherapy : CII
- Publication Type :
- Academic Journal
- Accession number :
- 15175905
- Full Text :
- https://doi.org/10.1007/s00262-004-0526-8