Neoplastic cells may express membrane-bound molecules, which they did not express before or only in low quantities, or mutated membrane molecules.
As a selective response to immune destruction, tumor cells may use several escape strategies, many of which involve down-regulation of Major histocompatibility complex molecules or other molecules implicated in the antigen-presentation pathway.
Such tumor cells do not express tumor-specific peptides on the outer membrane, and consequently they cannot be recognized by Cyto toxic lymphocytes(CTL).
Tumor cells may also directly inhibit the recognition or the function of immune cells by releasing immune inhibitory molecules.
However, cells other than CTL attack tumor cells: NK cells, polymorphonuclear leukocytes (PMN), and macrophages/DC do not recognize tumor cells via peptides.
These cells seem to be involved in the recently described, natural immunity against tumor cells.
Moreover, mice deficient in the innate immune system show higher incidence of tumor cell induction and outgrowth compared to wild-type mice.
Thus, cells from the innate immune system may play a role both in the destruction of the tumor cells and in the regulation of Major histocompatibility complex expression on cells with which they interact.
However, an important question in the discussion is whether the so-called selective response of tumor cells to immune destruction is (1) a global inductible response of all tumor cells, i.
e.
, the immune system induces the tumor cells to change character in such a way that the cancer cells become less sensitive to the immune effectors, or (2) a selective response of surviving tumor cells, i.
e.
, the immune effectors kill sensitive tumor cells but not mutated tumorigenic cells or the ones that have changed (down-regulated) certain characters, which render them invulnerable to the immune attack.
To activate the immune system, neoplastic cells must, in addition to the expression of tumor-associated antigens (TAA), induce cellular stress signals, danger signals, or damage-associated signals that alert the innate immune system.
Cell death, damage-associated molecular-pattern molecules, and endogenous danger signals are all associated with expression of heat-shock proteins, chromatin-associated protein high-mobility group box 1, and others.
This is followed by the expression of "eat me" signals and suppression of "don't eat me" signals on the "troubled" cells, which are then taken-up by immature Dendritic cells.
The consequence of the dendrocyte "troubled" cells interaction will greatly differ, depending on the necrotic versus apoptotic status of the "troubled" cells.
If the "troubled" cells are necrotic, then they release inflammatory molecules that induce the immature dendrocytes to mature and elicit cross-priming of the immune system.
Necrotic cell death releases HMGB1 and proteins derived from the tissue injury, such as hyaluronan fragments and nonprotein purinergic molecules such as ATP and uric acid, and induces inflammation due to IL-1b, IFNg, and Tumor necrosis factor.
Cell death, damage-associated molecular-pattern molecules activate cells of the innate immune system by triggering TLR or other alarm-signal receptors.
In contrast, if the immature Dendritic Cells take up "troubled" cells undergoing apoptotic cell death, they turn into tolerogenic dendrocytes due in part to the activity of caspases that render HMGB1 inactive.
This causes absence of induction of inflammation and no differentiation of immature Dendritic Cells to mature ones.
In addition to Cell death, damage-associated molecular-pattern molecules and endogenous danger signals, tumor cells may release effector molecules that stimulate the immune cells to collaborate in tumor growth in the sub-threshold neoplastic states.
The complement system, in particular properdin, seems to play an important role in this process by amplifying the production of reactive oxygen and nitrogen species by myeloid-derived suppressor cells.
In fact, growing neoplastic cells may be considered by the tissue as a physical wound, and the tissue response to such "intrusion" is wound healing.
This means attraction of stromal, endothelial, and epithelial cells, release of chemokines and cytokines as well as molecules of the blood-clotting system.
Thus, both normal repair systems, different danger signals, and the immune system may take part in the initiation process from a transformed neoplastic cell to an established, solid tumor.
Read more about Cancer Biology
As a selective response to immune destruction, tumor cells may use several escape strategies, many of which involve down-regulation of Major histocompatibility complex molecules or other molecules implicated in the antigen-presentation pathway.
Such tumor cells do not express tumor-specific peptides on the outer membrane, and consequently they cannot be recognized by Cyto toxic lymphocytes(CTL).
Tumor cells may also directly inhibit the recognition or the function of immune cells by releasing immune inhibitory molecules.
However, cells other than CTL attack tumor cells: NK cells, polymorphonuclear leukocytes (PMN), and macrophages/DC do not recognize tumor cells via peptides.
These cells seem to be involved in the recently described, natural immunity against tumor cells.
Moreover, mice deficient in the innate immune system show higher incidence of tumor cell induction and outgrowth compared to wild-type mice.
Thus, cells from the innate immune system may play a role both in the destruction of the tumor cells and in the regulation of Major histocompatibility complex expression on cells with which they interact.
However, an important question in the discussion is whether the so-called selective response of tumor cells to immune destruction is (1) a global inductible response of all tumor cells, i.
e.
, the immune system induces the tumor cells to change character in such a way that the cancer cells become less sensitive to the immune effectors, or (2) a selective response of surviving tumor cells, i.
e.
, the immune effectors kill sensitive tumor cells but not mutated tumorigenic cells or the ones that have changed (down-regulated) certain characters, which render them invulnerable to the immune attack.
To activate the immune system, neoplastic cells must, in addition to the expression of tumor-associated antigens (TAA), induce cellular stress signals, danger signals, or damage-associated signals that alert the innate immune system.
Cell death, damage-associated molecular-pattern molecules, and endogenous danger signals are all associated with expression of heat-shock proteins, chromatin-associated protein high-mobility group box 1, and others.
This is followed by the expression of "eat me" signals and suppression of "don't eat me" signals on the "troubled" cells, which are then taken-up by immature Dendritic cells.
The consequence of the dendrocyte "troubled" cells interaction will greatly differ, depending on the necrotic versus apoptotic status of the "troubled" cells.
If the "troubled" cells are necrotic, then they release inflammatory molecules that induce the immature dendrocytes to mature and elicit cross-priming of the immune system.
Necrotic cell death releases HMGB1 and proteins derived from the tissue injury, such as hyaluronan fragments and nonprotein purinergic molecules such as ATP and uric acid, and induces inflammation due to IL-1b, IFNg, and Tumor necrosis factor.
Cell death, damage-associated molecular-pattern molecules activate cells of the innate immune system by triggering TLR or other alarm-signal receptors.
In contrast, if the immature Dendritic Cells take up "troubled" cells undergoing apoptotic cell death, they turn into tolerogenic dendrocytes due in part to the activity of caspases that render HMGB1 inactive.
This causes absence of induction of inflammation and no differentiation of immature Dendritic Cells to mature ones.
In addition to Cell death, damage-associated molecular-pattern molecules and endogenous danger signals, tumor cells may release effector molecules that stimulate the immune cells to collaborate in tumor growth in the sub-threshold neoplastic states.
The complement system, in particular properdin, seems to play an important role in this process by amplifying the production of reactive oxygen and nitrogen species by myeloid-derived suppressor cells.
In fact, growing neoplastic cells may be considered by the tissue as a physical wound, and the tissue response to such "intrusion" is wound healing.
This means attraction of stromal, endothelial, and epithelial cells, release of chemokines and cytokines as well as molecules of the blood-clotting system.
Thus, both normal repair systems, different danger signals, and the immune system may take part in the initiation process from a transformed neoplastic cell to an established, solid tumor.
Read more about Cancer Biology