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 |