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Flashcards in Tumor Immunology (complete) Deck (22):

What is the Immune Surveillance theory?

In 1959 Lewis Thomas theorized that:

- T-cell mediate immune response evolved as a way to detect changes in the body's own cell surface
- Changes could be from damage or mutation
- If an abnormal cell was detected, T cells would destroy it before it could multiply (become malignant)

According to this theory:
- Cancer is a failure of the adaptive immune system


Do data from immunosuppressed and immunodeficient patients support the Immune Surveillance theory? Why/why not?


- Immunodeficient: those w/AIDS have ^ rate of Karposi sarcoma, Burkitt lymphoma, other tumors
- Immunosuppressed: Organ xplant recipients have 25-100x ^ in tumors
- Those w/ chemo: 14x ^ risk of secondary leukemia


Describe tumor-associated antigens (TAA)

Ag on/in tumor cell

Often in a normal cell but it's either overexpressed or abnormally expressed in tumor cells

Much lower quantities in normal cell


Describe viral gene products (cancer)

Some tumors are caused by viruses (e.g. HPV-related cancers, Burkitt lymphoma [EBV])

Preventing virus is key



Describe mutant gene products (cancer)

- Chemical/physical carcinogens lead to cellular transformation
- Mutated proteins processed/presented to immune system
- Mutations not always identical from pt to pt => immunotherapy designed against Ags may not be as generalizable as viral/normal gene products


What are oncofetal Ags?

- Made in normal fetal tissue
- Not found in normal tissue in adults => can be re-expressed in tumor


What are differentiation Ags?

- Lineage specific tumor Ags (e.g. ovarian, breast cancers)
- Most frequently identified TAA
- Overexpressed in specific tumors


What are clonal Ags?

- Expressed uniquely on malignant clone
- Eg: idiotype of surface Ig in B cell malignancies
- Give hope for vaccine development


Define carcinoembryonic antigen (CEA)

- A type of oncofetal Ag
- Found in blood of pts w/ colon and other cancers
- Was used as a screening tests
- But there were too many false positives


Discuss CEA's usefulness in screening for, diagnosis, and follow-up of colon cancer

- High false positives

However, useful for:
1) high suspicion of colon cancer
2) when that cancer has been removed => confirm complete excision
3) Warn of recurrent cancer after removal


Describe the role of CTL cells in killing tumors cells. Include reference to the amount of MHC Class I expressed by tumor

- CD8+ T cells
- Can recognize TAA presented by MHC class I
- Activated in lymph nodes (not tumor site) via APCs
- After, undergo clonal expansion & acquire lytic abilities
- Once activated => migrate to tumor
- Kills tumor cells by inducing apoptosis
- Also secrete IFN-gamma (attracts macros)


Describe the role of NK cells in killing tumors cells. Include reference to the amount of MHC Class I expressed by tumor

- usually called LGLs (large granular lymphocytes)
- part of innate immunity
- Recognize stressed-related markers on tumor cells w/ NK receptors
- Down-regulated if the target cell expresses Class I MHC (thinks it's CTL's job to take care of it)


Discuss the roles of PD-1 and CTLA-4 in regulating T cell (especially CTL) acitivity

Both inactivate/downregulate CTL


Discuss the use of monoclonal blocking Abs against PD-1 and CTLA-4 to prevent CTL down-regulation in tumor patients

PD-1: monoAb binds/blocks CTL inactivation by tumors that express PD-1 ligands

CTLA-4: similar mechanism but different monoAg


What are the principles underlying Ab methods that might be used as treatments of tumors?

- monoAbs => activate complement, tumor lysed/phagocytosed, ADCC
- Also used to tag or poison tumor cells


What are the principles underlying T cell methods that might be used as treatments of tumors?

- Adoptive cell transfer therapy

not sure what else to say... sorry guys


Describe a mechanism by which BCG treatment causes tumor regression

- BCG is injected directly into tumor
- Delayed-type hypersensitivity rxn starts => tumor cells are killed as innocent bystanders
- Tx of choice in superficial bladder carcinoma


Describe the nature and therapeutic use of tumor-infiltrating lymphocytes (TIL) in adoptive cellular transfer therapy

TIL: cells directly from tumor

- Use pt's immune system to destroy cancerous cells
- T cells are expanded in culture using cytokines
- Pt's immune system is partially destroyed to make room for these add'l T cells


What is immunoediting? What are the three stages of immunoediting?

Role of immune system in neoplastic development

1) Elimination
2) Equilibrium
3) Escape


Describe the elimination stage of immunoediting

There are always new mutations in our body, but our immune system is constantly eliminating them

- Malignant clone => recognized by innate & adaptive immune system => eliminated
- DAMPs recognize metabolic abnormalities of tumor cells
- DCs activate T cells => macros and CTLs infiltrate tumor

Process ends here if eradicated


Describe the equilibrium stage of immunoediting

- T/B cells infiltrate tumor => doesn't destroy it (EQUILIBRIUM)
- Analogous to latency
- However, one's immunity can drop for some reason => more mutations in tumor cells => reactivation


Describe the escape stage of immunoediting

Tumor cells fight back!
- Tumor-specific CTLs sometimes can't fully kill the tumor
- CTLs have >2 check point inhibitor surface receptors (CTLA-4 and PD-1) => if tumor cells interact with them => downregulation of cytotoxic activity
- Tumor cells that escape CTLs become resistant to them => create an entire tumor of CTL-resistant cells

1) Suppress the immune system
2) Create decoys (become invisible)