Tumor Immune Evasion

Question 1

What do MHC 1 and 2 present, respectively

Answer 1

MHC 1 = Present on all nucleated cells
Presents cytosolic proteins (infected) that are degraded by proteasome.
MHC 1 is recognized CD8-killer cells. Important molecule is TAP that load the peptide on MHC 1 which is bound on ER and thereby allowing transport of MHC 1 to surface

MHC 2 = Only present on professional APC
Present microbes that have been phagocyted
MHC 2 is recognized by CD4-helper cells
Endosome with foreign peptide is fused with endosome of MHC 2 molecule and the invariant chain is changed with the foreign antigen and expressed at the surface

Question 2

The IS recognize tumor antigens, what are these

Answer 2

• Differentiation antigens, not expressed on mature cells
• Over-expressed antigens, normal proteins
• Tumor specific antigens, unique or shared antigens, point mutated proteins, virus antigens (HBV)

Question 3

Which 2 ways can the tumor evade the IS

Answer 3

• Immune Escape by getting invisible or inducing tolerance

- Immunosuppression of the host

Question 4

How do the tumor escape the IS

Answer 4

Become “invisible” –>

• The tumor cell can down-regulate the tumor-antigen to be expressed unless its important for its own proliferation
• It can mess with the MHC presentation by interfering with TAP molecule so less MHC is presented

Induce Tolerance –>

• Non-mutated tumors have some tolerance due to central tolerance. However if some mutation occur it should be a reaction due to new antigen.
• Interfering with sign.2, deregulate the co-stimulatory receptors during Antigen presentation so T cell go into anergy or Tregs
• Danger hypothesis; low levels of inflammation without danger signal cause progression of cancer cell

Question 5

Hos do Tumors suppress the host IS

Answer 5

• Tumors secrete immunosuppressive substances; IL-10, TGF-b, IDO etc.
• Tumors induce Treg differenatiation in some way..
• FasL expression on tumors cells doesn’t work