Abstract
Lymph nodes represent critical lymphoid compartments where antigen-presenting cells interact with T cells to propagate cellular immune responses. As such, they represent a unique source of “pre-effector” T cells that can be induced by the regional inoculation of tumor antigen as a vaccine. Utilizing this concept, we have been able to generate tumor-reactive T cells from vaccine-primed lymph nodes (VPLNs) that can mediate tumor regression in adoptive immunotherapy. This chapter describes how this pre-effector response in VPLNs can be suppressed by the presence of established systemic tumor. This suppression involves the B7-H1/PD-1 axis as well as TGF-β. Methods to block these suppressive mechanisms will be important in improving future adoptive cellular therapy approaches.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Stephenson KR, Perry-Lalley D, Griffith KD, Shu S, Chang AE. Development of antitumor reactivity in regional draining lymph nodes from tumor-immunized and tumor-bearing murine hosts. Surgery 1989; 105(4):523–8.
Yoshizawa H, Chang AE, Shu S. Specific adoptive immunotherapy mediated by tumor-draining lymph node cells sequentially activated with anti-CD3 and IL-2. J Immunol 1991; 147(2):729–37.
Tanigawa K, Takeshita N, Eickhoff GA, Shimizu K, Chang AE. Antitumor reactivity of lymph node cells primed in vivo with dendritic cell-based vaccines. J Immunother 2001; 24(6):493–501.
Geiger JD, Wagner PD, Cameron MJ, Shu S, Chang AE. Generation of T-cells reactive to the poorly immunogenic B16-BL6 melanoma with efficacy in the treatment of spontaneous metastases. J Immunother Emphasis Tumor Immunol 1993; 13(3):153–65.
Strome SE, Krauss JC, Cameron MJ, Forslund K, Shu S, Chang AE. Immunobiologic effects of cytokine gene transfer of the B16-BL6 melanoma. Arch Otolaryngol Head Neck Surg 1993; 119(12):1289–95.
Arca MJ, Krauss JC, Aruga A, Cameron MJ, Shu S, Chang AE. Therapeutic efficacy of T cells derived from lymph nodes draining a poorly immunogenic tumor transduced to secrete granulocyte-macrophage colony-stimulating factor. Cancer Gene Ther 1996; 3(1):39–47.
Chang AE, Li Q, Bishop DK, Normolle DP, Redman BD, Nickoloff BJ. Immunogenetic therapy of human melanoma utilizing autologous tumor cells transduced to secrete granulocyte-macrophage colony-stimulating factor. Hum Gene Ther 2000; 11(6):839–50.
Aruga A, Shu S, Chang AE. Tumor-specific granulocyte/macrophage colony-stimulating factor and interferon gamma secretion is associated with in vivo therapeutic efficacy of activated tumor-draining lymph node cells. Cancer Immunol Immunother 1995; 41(5):317–24.
Aruga A, Aruga E, Tanigawa K, Bishop DK, Sondak VK, Chang AE. Type 1 versus type 2 cytokine release by Vbeta T cell subpopulations determines in vivo antitumor reactivity: IL-10 mediates a suppressive role. J Immunol 1997; 159(2):664–73.
Tanigawa K, Takeshita N, Craig RA, et al. Tumor-specific responses in lymph nodes draining murine sarcomas are concentrated in cells expressing P-selectin binding sites. J Immunol 2001; 167(6):3089–98.
Li Q, Yu B, Grover AC, Zeng X, Chang AE. Therapeutic effects of tumor reactive CD4+ cells generated from tumor-primed lymph nodes using anti-CD3/anti-CD28 monoclonal antibodies. J Immunother 2002; 25(4):304–13.
Li Q, Carr A, Ito F, Teitz-Tennenbaum S, Chang AE. Polarization effects of 4-1BB during CD28 costimulation in generating tumor-reactive T cells for cancer immunotherapy. Cancer Res 2003; 63(10):2546–52.
Kroon HM, Li Q, Teitz-Tennenbaum S, Whitfield JR, Noone AM, Chang AE. 4-1BB costimulation of effector T cells for adoptive immunotherapy of cancer: involvement of Bcl gene family members. J Immunother 2007; 30(4):406–16.
Chang AE, Aruga A, Cameron MJ, et al. Adoptive immunotherapy with vaccine-primed lymph node cells secondarily activated with anti-CD3 and interleukin-2. J Clin Oncol 1997; 15(2):796–807.
Chang AE, Li Q, Jiang G, Sayre DM, Braun TM, Redman BG. Phase II trial of autologous tumor vaccination, anti-CD3-activated vaccine-primed lymphocytes, and interleukin-2 in stage IV renal cell cancer. J Clin Oncol 2003; 21(5):884–90.
Curiel TJ, Coukos G, Zou L, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004; 10(9):942–9.
Zou W. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 2005; 5(4):263–74.
Chen L. Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol 2004; 4(5):336–47.
Sharpe AH, Freeman GJ. The B7-CD28 superfamily. Nat Rev Immunol 2002; 2(2):116–26.
Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med 1999; 5(12):1365–9.
Curiel TJ, Wei S, Dong H, et al. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 2003; 9(5):562–7.
Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 2006; 6(4):295–307.
Shimizu J, Yamazaki S, Sakaguchi S. Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J Immunol 1999; 163(10):5211–8.
Onizuka S, Tawara I, Shimizu J, Sakaguchi S, Fujita T, Nakayama E. Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res 1999; 59(13):3128–33.
Sutmuller RP, van Duivenvoorde LM, van Elsas A, et al. Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. J Exp Med 2001; 194(6):823–32.
Chen W, Jin W, Hardegen N, et al. Conversion of peripheral CD4+CD25– naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 2003; 198(12):1875–86.
Fantini MC, Becker C, Monteleone G, Pallone F, Galle PR, Neurath MF. Cutting edge: TGF-beta induces a regulatory phenotype in CD4+CD25– T cells through Foxp3 induction and down-regulation of Smad7. J Immunol 2004; 172(9):5149–53.
Wan YY, Flavell RA. Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter. Proc Natl Acad Sci USA 2005; 102(14):5126–31.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Humana Press, a part of Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Wei, S., Shreiner, A.B., Chang, A.E. (2009). Vaccine-Primed Lymph Node Cells in the Adoptive Immunotherapy of Cancer: Presence of Host Immune Suppression Induced by Established Cancer. In: Leong, S. (eds) From Local Invasion to Metastatic Cancer. Current Clinical Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-087-8_36
Download citation
DOI: https://doi.org/10.1007/978-1-60327-087-8_36
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-60327-086-1
Online ISBN: 978-1-60327-087-8
eBook Packages: MedicineMedicine (R0)