Table 1.

Mechanisms orchestrated by the tumor that contribute to its escape from the host immune system^a

A. Interference with the induction of anti-tumor immune responses:

1. Decreased expression of costimulatory molecules on the tumor or APC

2. Alterations in TCR signaling in TIL

3. Death receptor/ligand signaling and `tumor counterattack'

3. Dysfunction of DC and inadequate cross-presentation of TAA to T cells

4. DC apoptosis in the tumor microenvironment

B. Inadequate effector cell function in the tumor microenvironment:

1. Suppression of T-cell responses by Treg

2. Suppression of immune cells by myeloid suppressor cells (MSC)

3. Apoptosis of effector T cells in the tumor and in the periphery

4. Microvesicles (MV, exosomes) secreted by human tumors and inducing apoptosis of CD8+ effector T cells

C. Insufficient recognition signals:

1. Downregulation of surface expression of HLA molecules on tumor cells

2. Downregulation of surface TAA displayed by tumor cells: antigen loss variants

3. Alterations in APM component expression in tumor cells or APC

4. Suppression of NK activity in the tumor microenvironment

D. Development of immunoresistance by the tumor:

1. Lack of susceptibility to immune effector cells

2. Immunoselection of resistant variants

3. Tumor stem cells

^aThe table lists the mechanisms selected from among others known to illustrate the diversity of escape strategies used by human tumors. A more detailed description of these mechanisms can be found in the reference by Whiteside, 2006.