cancer and immune system
The immune system plays a role in surveillance of neoplastic cells that have escaped controls on proliferation. In their turn, tumors employ a variety of mechanisms to evade the immune system.
Some tumors have tumor-specific antigens on their surfaces. (These antigens are also called TSA, tumor-specific transplantation antigens, TSTA, tumor rejection antigens, or TRA.) TSA are absent on non-tumor cells, and typically appear after an infecting virus has caused the cell to express viral antigens and to become immortal. Some TSAs are not induced by viruses, are are the idiotypes of BCR on B cell lymphomas or TCR on T cell lymphomas. [table]
Tumor-associated antigens (TAA) are more common than TSA. These T antigens are found on tumor cells and on normal cells during fetal life (onco-fetal antigens), after birth in selected organs, or in many cells at a considerably lower concentration than on tumor cells. Because of the presence of these antigens on various normal cells, the immune responses to TAA may be suppressed because they are tolerated as "self".
Evasive mechanisms range from a passive failure to express major histocompatibility complexes (MHC) and co-stimulatory molecules 4,5 to active strategies such as the production of immunosuppressive cytokines and other factors 6,7 . Passive and active processes are also involved in the Fas counterattack.[s]
Tumor cells can present only self peptides or can downregulate Class I MHC expression. Tumor cells often fail to express co-stimulatory molecules such as B7, or do not produce adhesion molecules that are necessary for interaction with CD8 T cells.
Tumors can also avoid immune system attack by down-regulating expression of their tumor antigens or by spontaneously alter their structure (antigenic variation).
Ironically, antibodies to tumor surface antigens could promote tumor survival (enhancing antibodies) should the antibodies bind without eliciting cytotoxicity – by masking the tumor antigens from T cells while inducing tumor cells to down-regulate expression of tumor antigen.
Some tumors actively suppress the immune response by producing TGFβ, which is a suppressive cytokine that inhibits cellular immunity. Some tumors, including myeloma and HTLV-1 T cell leukemia, also produce cytokines that stimulate their own proliferation.
The Fas ligand (FasL, C95L) is expressed by cells of the lymphoid/myeloid series and by non-lymphoid cells, where it contributes to the 'immune privilege' of cancer cells by inducing apoptosis in infiltrating proinflammatory immunocytes 9,10. Simultaneously, many cancer cells are relatively resistant to Fas-mediated apoptosis.
This resistance to Fas-mediated apoptosis might be a result of downregulation of Fas, or release of soluble Fas, or of abnormalities in the level of several signal transduction cascade proteins. Neoplastic Fas resistance might also result from downregulation of caspase 1, Bax or Bak, and upregulation of FLIP, FAP-1 or Bcl2. Further, some components of the pathway exhibit mutations, including Fas itself and caspase 8. Some mutations of oncogenes and tumor suppressor genes, which are commonly found in tumors, could impair Fas signaling (p53 and Ras) or could cooperate with Fas resistance (c-Myc) in certain tumor cells. Many cancer cells express FasL, so are able to counterattack and kill Fas-sensitive tumor- infiltrating lymphocytes (TILs).[s]
¤ carcinogenesis ¤ immune evasion ¤ malignant transformation ¤ metastasis ¤ oncogenes ¤ p53 ¤ proliferation ¤ proto-oncogenes ¤ Ras ¤ signaling molecules ¤
Malignant Transformation Oncogenes Proto-oncogenes Regulatory Proteins Sequences Apoptosis vs Necrosis Apoptosis Tables Fc receptors Immune Cytokines Immunoglobulins Cell Adhesion Molecules Cell signaling Receptor Tyrosine Kinases (RTKs) Receptor Signal Transduction Second Messengers
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tags [Immunology][cancer]
