Table 4 Known or possible obstacles to immunologic control of tumor progression, which impact on both active immunotherapy (cancer vaccines) and adoptive immunotherapy.
From: Progress and controversies in developing cancer vaccines
| 1) Expression of tumor antigens in the absence of costimulatory molecules on tumor cells, leading to tolerance |
|---|
| 2) Chronic antigen exposure, leading to upregulation of immuno-regulatory mechanisms |
| a) CTLA4 expression |
| b) Accumulation of regulatory T cells in the tumor microenvironment |
| 3) Downregulation of MHC molecule expression by tumor cells |
| 4) Downregulation of tumor antigen expression by tumor cells |
| 5) Secretion of anti-inflammatory cytokines by tumor cells or tumor-associated stroma |
| a) IL-10 |
| b) TGF-β |
| c) Others |
| 6) Expression of enzymes in the tumor microenvironment that interfere with T cell function |
| a) Arginase |
| b) Indoleamine 2,3-dioxygenase (IDO) |
| 7) Propogation of a tumor microenvironment that is hostile to T cell activation |
| a) Immunoregulatory function of dendritic cells |
| b) Anergic tumor-infiltrating lymphocytes |
| 8) Tumor-associated VEGF and other neovascularity-enhancing mechanisms may have immunoregulatory properties as well. |
| 9) Homeostatic mechanisms in the host may limit expansion of tumor-specific T cell responses, and may limit expansion and persistence of tumor-specific T cell responses. |
| 10) Resistance of tumor cells to apoptosis |
| 11) Elaboration of compounds associated with tumor necrosis, that inhibit anti-tumor immunity locally |