Tumour Immunity Flashcards
how do cancer cells evade detection and elimination by the immune system?
- cancer cells are self-cells that have undergone transformation, making them harder for the immune system to recognize and eliminate
- normally, the body is very effective at identifying and killing abnormal or damaged cells
- however, cancer occurs when these transformed cells evade or hide from the immune system, allowing them to survive, proliferate, and spread
normal vs transformed cells
normal cells:
- normal cells have a finite life span
- they differentiatem function, and ultimately undergo apoptosis when too old to function
- macrophages will take up apoptotic bodies
transformed (cancer) cells:
- these cells have undergone mutations (either born with it or through damage)
- they have lost control of their cell cycle and enter mitosis at an uncontrolled rate
- this leads to a build up of uncontrolled proliferation, leading to tumour establishment
How do tumour cells evade the immune system and contribute to the spread and establishment of cancer?
- tumour cells are healthy body cells (not infected), so they express self molecules and appear as self cells (because they are).
- malignant tumors metastasize (spread) to other parts of the body when cells break off and move to another area, where they build up.
- established tumors are immunosuppressive, meaning they can hide and shut down the immune response.
how do tumour cells avoid the immune system?
tumour cells can undergo mutation in their genome to avoid immune system
- they can avoid recognition by down-regulating their MHC class I molecules
- they can resist destruction by up-regulating anti-apoptotic molecules
- they can actively suppress the immune system by activating anti-inflammatory cells and mediators
what are tumour antigens?
- tumours can produce antigens that are unique to the tumour cells, known as tumour-specific antigens.
- tumour antigens are expressed on the surface of tumour cells by MHC class I molecules
4 ways tumor antigens arise
1) tumor cells express brand new proteins not found in normal cells (novel antigens).
2) tumor cells express mutations of normal self-proteins, which cause them to look different due to genetic mutations.
3) tumor cells express antigens that are normally not expressed at the individual’s age
4) tumor cells express a higher level of self-antigens than normal, resulting in an abnormal amount of a normal antigen.
what are the 2 categories of tumor antigens?
- tumor specific antigens (TSA)
- tumor associated antigens (TAA)
compare and contrast TSA vs TAA
Tumor Specific Antigens (TSA):
- Unique antigens expressed only on tumor cells.
- not found on normal cells in the body.
- not very common (or don’t have tools to detect)
- m ay include viral antigens
Tumor Associated Antigens (TAA):
- not unique to tumors
- antigens normally expressed at low levels in normal cells, but are expressed at high levels on tumor cells.
- some antigens are expressed on normal cells during fetal development but are not expressed in adult cells
3 ways that the immune system can control cancer cells
1) identify and destroy viruses that cause cancer
- some viruses are cancer-causing
2) effective removal of pathogens quickly to reduce chronic inflammation
- prolonged inflammation can create an environment conducive to cancer development.
3) identify and eliminate tumor cells (immunosurveillance)
- the immune system should regularly identify and destroy abnormal or cancerous cells before they can proliferate and spread
the first two should always be happening all the time anyways
how do tumors evade immune recognition through MHC class I-related mechanisms?
-tumors can down-regulate or lose expression of MHC class I molecules, which are responsible for presenting tumor antigens to T-cells.
- without MHC class I, the immune system is unable to recognize the tumor cell as abnormal.
- tumors can also secrete tumor-specific antigens (TSA) into the extracellular space rather than presenting them on MHC class I.
- TAP or Beta2-microglobulin (B2M) can mutate and become ineffective:
–> if TAP is defective (peptide transporter), antigen processing is impaired, leading to reduced presentation of tumor antigens on MHC class I molecules on cancer cells.
–> defective B2M can result in a lack of functional MHC class I molecules on the surface of tumor cells, as B2M is a part of the MHC class I structure.
what are tumor vaccines?
- many therapeutic vaccines have been developed to promote anti-tumor immunity and destruction of tumor cells
- therapeutic vaccines occur after an individual already has cancer to try and “wake up” the immune system to recognize tumor cells
what were the types of tumor vaccines?
1) using whole tumor cells or peptides
- tumor cells or peptides derived from tumor cells are cultured in vitro and then injected back into the body as vaccines to trigger an immune response.
2) using tumor-specific antigens (TSA)
- vaccines can be designed to target tumor-specific antigens, which are unique to cancer cells, to stimulate the immune system to recognize and attack the tumor.
3) increase number of dendritic cells
- DCs activate long-lasting T-cell responses against tumors, helping generate memory cells for more effective tumor recognition and destruction.
do tumor vaccines work?
NO
- tumors have a number of strategies to evade/hide from immune responses, so even if we try to train the immune system, tumor can still shut it down
- tumors can exhibit a high level of antigenic diversity, meaning that the same tumor type in different individuals may have different mutations = diversity
- t-cell responses are MHC restricted, meaning that the effectiveness of a tumor vaccine can depend on the individual’s specific MHC haplotype
–> since people have different MHC alleles, a vaccine that works for one person may not be effective for someone with a different MHC genotype.
what are strategies for successful tumor vaccine?
to be successful, tumor vaccines need to overcome the low immunogenicity/tolerance of the tumor microenvironment and activate T cells at the same time
How to do this?
- Combine the tumor vaccine with an existing vaccine
- Add cytokines to promote antigen presentation and T cell activation
- Add an adjuvant that promotes co-stimulation molecule expression
what are cancer immunotherapies?
- a treatment that uses the body’s immune system to fight cancer
- immunotherapy can stop or slow cancer growth, prevent cancer from spreading, or deliver toxins directly to cancer cells
- works by stimulating or suppressing the immune system
chemotherapy is still the gold standard - but it targets dividing cells so causes lots of side effects
