(Burnet, 1970) More recent evidence has suggested that immunosurveillance is only part of a larger role the immune system plays in fighting cancer.
This experiment provides clear evidence that the immune system does, in fact, play a role in eradication of tumor cells.
[citation needed] As the name implies, the escape phase is characterized by a reduced immunogenicity of the cancer cells, their subsequent evasion of the immune system and their ability to be clinically detected.
(Dunn et al., 2004) Tumor cells may, through mutations, often begin producing large quantities of inhibitory cytokines IL-10, or transforming growth factor β (TGF-β) (Khong and Restifo, 2002) thereby suppressing the immune system, allowing for large-scale proliferation (Salazar-Onfray et al., 2007).
These T cells produce high levels of IL-10 and TGF-β, thereby suppressing the immune system and allowing for evasion by the tumor (Shimizu et al., 1999).
[1] Of note, results from recent reports suggest that direct recognition of tumors from tumor-antigen specific CD4+ T cells might not be always beneficial.
TNF may in turn increase local immunosuppression and impair the effector functions of CD8 T cells (Donia M. et al., 2015).
[2] The same series of experiments, examining the role of CD4+ cells, showed that high levels of IL-4 and IFNγ were present at the site of the tumor, following vaccination, and subsequent tumour challenge.
Activated macrophages produce IL-12, and since IL-12 promotes Th1 cell differentiation, this forms a tumor-suppressing feedback loop.
Th17 cells can orchestrate chronic inflammatory responses, which tend to promote tumor growth and survival.
[7] In addition, some tumors have been shown to express high levels of IL-6 & TGF-β, which would reinforce a Th17 polarization, creating a tumor-promoting feedback loop.
iNOS (inducible nitric oxide synthase) is an enzyme responsible for the production of NO, an important molecule used by macrophages to kill infected cells.
(Hung et al., 1998) Similar results have been seen in knockout mice deficient in gp91phox, a protein involved in the production ROIs (Reactive Oxygen Intermediates) which are also an important weapon utilized by macrophages to elicit cell death.
A series of experiments showed that it was essential for nonhematopoietic cells at the site of challenge, to express functional IFNγ receptors.
(Qiu, 1999) Mice vaccinated with irradiated strains of these cells show a greater immune response to subsequent challenge by the same tumor, without the upregulation of MHC class II, then do mice vaccinated with irradiated, but otherwise unaltered tumor cells.
Most recognized tumor antigens are endogenously produced, altered gene products of mutated cells.
Due to the extremely polymorphic nature of MHC class II molecules, simple transfection of these proteins does not provide a practical method for use as a cancer vaccine.
(Trincheiri and Perussia, 1985, Fransen L, 1986) A second, more effective approach involves targeting the genes responsible for the synthesis of these proteins, the CIITA or class II transcription activator.
upregulation of CIITA also causes an increased expression of Ii, and as such, must be used in conjunction with the antisense techniques referred to earlier (Qui, 1999).
In some forms of cancer, such as acute myeloid leukemia (AML) the cells may already be MHC class II+, but because of mutation, express low levels on their surface.