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Adoptive Immunotherapy

Adoptive Immunotherapy. The transfer of cells, with antitumor reactivity, to the tumor bearing host which can directly or indirectly mediate antitumor effects. A form of passive immunotherapy. Source of Immune Cells. Blood Tumor Lymph nodes. Tumor-infiltrating lymphocytes (TIL).

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Adoptive Immunotherapy

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  1. Adoptive Immunotherapy The transfer of cells, with antitumor reactivity, to the tumor bearing host which can directly or indirectly mediate antitumor effects. A form of passive immunotherapy

  2. Source of Immune Cells • Blood • Tumor • Lymph nodes

  3. Tumor-infiltrating lymphocytes (TIL)

  4. Despite the ability to generate a cellular or humoral immune response, the therapeutic efficacy of immune treatments have been limited.A key question is why? What mechanisms result in immune evasion?

  5. Suppressive Immune Elements • Regulatory T cells • Regulatory dendritic cells • Cytokines: IL-10, TGF-β, VEGF • Suppressive factors: arginase, IDO • Co-inhibitory signals between APC and T cells: CTLA4, B7-H1/PD-1, B7-H4 • Down-regulation of tumor antigen expression/presentation • Stat 3 signalling in tumors

  6. Regulatory T cells (Tregs) A regulatory T cell is functionally defined as a T cell that inhibits an immune response by influencing the activity of another cell type. The classic regulatory T cell is a CD4+CD25+FoxP3+ cell.

  7. FOXP3+CD25+ cells in tumors Death Kiss

  8. T cell subsets imbalance and tumor immunity Effector T cells Regulatory T cells TAA-specific effector CTL TAA-specific effector CD4+ T cells IL10+CD8+ suppressive T cells CD4+CD25+ suppressive T cells Tumor microenvironment Tumor immunity

  9. Treg Levels and Ovarian Cancer Survival Zou and co-workers, Nat Med 10: 942-49, 2004

  10. Tumor Tregs and survival 1. Tumor CD4+ Tregs are detrimental to TAA-immunity 2.Tumor CD4+ Tregs are a prognostic factor for patients survival 3. Killing Tregs may be therapeutically meaningful

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