Immunomodulation of Breast Cancer via Tumor Antigen Specific Th1
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It has long been assumed that the immune system plays a role in tumor eradication, however, scant clinical evidence exists to support that hypothesis. In recent years, as the immune system and its specific effector cells are better defined, convincing data supporting immune surveillance is emerging. Several studies have shown that an “immune signature” in the tumor microenvironment is associated with a superior outcome in a variety of cancer types. Moreover, studies have suggested that T cells found in high density within the tumor parenchyma are also correlated with a survival benefit. The type of adaptive immune response implicated in improved cancer outcomes is a type 1 response. That is, adaptive immunity associated with T cells that secrete pro-inflammatory cytokines, such as IFN-γ, which can not only support a proliferative antigen specific T cell response but also enhance “cross priming” by activating antigen presenting cells local to the tumor site. There are many methods available that will allow the development of clinical reagents designed to stimulate Th1 immunity; either by in vitro or in vivo manipulation. Clinical trials of a variety of immunotherapeutic strategies indicate that the generation of tumor antigen specific Th1 may be beneficial in inhibiting the growth of common solid tumors.
Abstract
It has long been assumed that the immune system plays a role in tumor eradication, however, scant clinical evidence exists to support that hypothesis. In recent years, as the immune system and its specific effector cells are better defined, convincing data supporting immune surveillance is emerging. Several studies have shown that an “immune signature” in the tumor microenvironment is associated with a superior outcome in a variety of cancer types. Moreover, studies have suggested that T cells found in high density within the tumor parenchyma are also correlated with a survival benefit. The type of adaptive immune response implicated in improved cancer outcomes is a type 1 response. That is, adaptive immunity associated with T cells that secrete pro-inflammatory cytokines, such as IFN-γ, which can not only support a proliferative antigen specific T cell response but also enhance “cross priming” by activating antigen presenting cells local to the tumor site. There are many methods available that will allow the development of clinical reagents designed to stimulate Th1 immunity; either by in vitro or in vivo manipulation. Clinical trials of a variety of immunotherapeutic strategies indicate that the generation of tumor antigen specific Th1 may be beneficial in inhibiting the growth of common solid tumors.
참고문헌 (30)
- Coussens LM, "Inflammation and cancer", Nature, 420, pp.860~867
- Banchereau J, "Dendritic cells as therapeutic vaccines against cancer", Nat Rev Immunol, 5, pp.296~306 (2005)
- AUA, "American Urologic Association Annual Meeting" (2009)
- Schuster S, "Idiotype vaccine therapy (BiovaxID) in follicular lymphoma in first complete remission: phase III clinical trial results", J Clin Oncol, 27 (2009)
- Galon J, "Type, density, and location of immune cells within human colorectal tumors predict clinical outcome", Science, 313, pp.1960~1964 (2006)
- Kreike B, "Gene expression profiling and histopathological characterization of triplenegative", basal-like breast carcinomas, 2007, pp.9, R65~
- Roepman P, "An immune response enriched 72-gene prognostic profile for early-stage non-small-cell lung cancer", Clin Cancer Res, 15, pp.284~290 (2009)
- Zhang L, "Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer", N Engl J Med, 348, pp.203~213 (2003)
- Cohen PA, "CD4+ T cells in adoptive immunotherapy and the indirect mechanism of tumor rejection", Crit Rev Immunol, 20, pp.17~56 (2000)
- Vanderlugt CL, "Epitope spreading in immune-mediated diseases: implications for immunotherapy", Nat Rev Immunol, 2, pp.85~95 (2002)
- Knutson KL, "Immunization of cancer patients with a HER-2", neu, HLA-A2 peptide, p369-377, results in short-lived peptide-specific immunity, 2002, pp.8, 1014~1018
- Disis ML, "Generation of T-cell immunity to the HER-2", neu protein after active immunization with HER-2, J Clin Oncol, pp.2002, 20[DOI]
- Disis ML, "Generation of immunity to the HER- 2", neu oncogenic protein in patients with breast and ovarian cancer using a peptidebased vaccine, 1999, pp.5, 1289~1297
- Salazar LG, "Immunization of cancer patients with HER-2", neu-derived peptides demonstrating high-affinity binding to multiple class II alleles, 2003, pp.9, 5559~5565
- Park KH, "Insulin-like growth factorbinding protein-2 is a target for the immunomodulation of breast cancer", Cancer Res, 68, pp.8400~8409 (2008)
- Lu J, "Use of two predictive algorithms of the world wide web for the identification of tumor-reactive T-cell epitopes", Cancer Res, 60, pp.5223~5227 (2000)
- Disis ML, "Granulocytemacrophage colony-stimulating factor: an effective adjuvant for protein and peptidebased vaccines", Blood, 88, pp.202~210 (1996)
- Napolitani G, "Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells", Nat Immunol, 6, pp.769~776 (2005)
- Kaiko GE, "Immunological decision-making: how does the immune system decide to mount a helper T-cell response?", Immunology, 123, pp.326~338 (2008)
- Butterfield LH, "Determinant spreading associated with clinical response in dendritic cell-based immunotherapy for malignant melanoma", Clin Cancer Res, 9, pp.998~1008 (2003)
- Salazar LG, "Persistent immunity and survival after immunization with a HER2", neu (HER2) vaccine, 2009, pp.27, ~
- Disis ML, "Concurrent trastuzumab and HER-2", neu specific vaccination in patients with metastatic breast cancer, 2009, ~
- Knutson KL, "Immunization with a HER-2", neu helper peptide vaccine generates HER-2, J Clin Invest, pp.2001, 107[DOI]
- Disis ML, "Pre-existent immunity to the HER-2", neu oncogenic protein in patients with HER-2, Breast Cancer Res Treat, pp.2000, 62[DOI]
- Arnould L, "Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?", Br J Cancer, 94, pp.259~267 (2006)
- Nakai N, "Immunoregulatory T cells in the peripheral blood of melanoma patients treated with melanoma antigenpulsed mature monocyte-derived dendritic cell vaccination", J Dermatol Sci, 54, pp.31~37 (2009)
- Disis ML, "Phase I study of infusion of HER2", neu (HER2) specific T cells in patients with advanced-stage HER2 overexpressing cancers who have received a HER2 vaccine, 2009, pp.27, ~
- Dang Y, "Tumor antigen-specific T-cell expansion is greatly facilitated by in vivo priming", Clin Cancer Res, 13, pp.1883~1891 (2007)
- Knutson KL, "IL-12 enhances the generation of tumour antigen-specific Th1 CD4 T cells during ex vivo expansion", Clin Exp Immunol, 135, pp.322~329 (2004)
- Dudley ME, "Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma", J Clin Oncol, 23, pp.2346~2357 (2005)