Flashcards in Tumor immunology Deck (31):
What is immune surveillance theory?
True role of T cells to constantly monitor surface of body cells and destroy abnormal cells before mutant/possible malignant clone develops
What evidence supports immune surveillance theory?
Immunodeficient/suppressed people have
1) high incidence of tumors
2) lymphocytes in tumors is good prognostic indicator
3) small percentage of tumors spontaneously regress
What evidence against immune surveillance theory?
1) Do not get random sample of all tumors possible
2) nude mice (no thymus) have no increase in tumors
What is immunoediting?
Immune system's role in development of tumors
3 parts of immunoediting- Elimination
Most cells init by mutagenic events recognized and stim by innate/adaptive immune sys
tumor cells exhibit metabolic abnormalities --> expression of DAMPs --> activate innate immunity
3 parts of immunoediting- equilibrium
T cells enter tumor and in equal with tumor rather than destroying tumor (tumor and lymphocytes in equilbrium)
keeps tumor in latency until sudden drop in immune response or incr tumor cell mutations
3 parts of immunoediting- Escape
Tumors escaping immune system
1) blocking factors
2) modification of tumor assoc antigens
3) production of immunosuppressive factors
4) reduced expression of MHC 1
What are tumor associated antigens?
Antigens that are abnormally expressed or over expressed on tumor cells
What are tumor rejection antigens
TAA recognized by immune system and lead to cell destruction
TAA from viral gene products
Predictable and generalized based on infecting virus (cervical cancer TAA from HPV)
TAA from mutant gene products
Tumor specific antigens
Random unpredictable mutations to cellular porteins
TAA from normal gene products
what are oncofetal antigens?
antigens made in normal fetal tissue re-expressed in adult blood with cancers (carcinoembryonic antigen in colon cancer pts)
what are differentiation antigens
lineage specific antigens over expressed in tumors (HER-2 in breast/PSA in prostate)
what are clonal antigens
TAA uniquely expressed by malignant cells (not normal cells) --> idiotypes of surface immunoglobulins/T cell receptors
What is carcinoembryonic antigen?
Oncofetal antigen normally found in fetal tissue but re-expressed in adults with colon CA
Should CEA be used as screening test?
NO because high likelihood of false positive
Should CEA be used in diagnosing colon cancer?
also CEA levels used to determine efficacy of excision of tumor (0 = complete excision; rising = recurrence)
Role of CTL in killing tumor cells
CTL = most importance in tumor resistance
1) activated in lymph node
2) clonal expansion and migrate to tumor
3) interact with TAA presented by MHC 1
4) induce apoptosis of Tumor cell
5) secrete IFN-g --> stim macrophages
How do tumor cells escape immune system?
Reduced expression of MHC 1
Role of NK cells in killing tumor cells
NK cells have receptor for stress marker on growth-dysregul cells and Fc for IgG on tumor cell
used to kill tumor cells that downregul MHC 1
What is TIL
Cells taken from tumor of a patient
expanded in culture with IL-2
Role of tumor infiltrating lymphocytes (TIL) in adoptive cellular transfer therapy
1) destroy pt's immune system with radiation
to make room for expanded clone
Cells from tumor should have increased potential to fight tumor
Discuss the role of PD-1 and CTLA-4 in regulating T cell (specifically CTL) activity, and the use of monoclonal blocking antibodies against these receptors to prevent CTL down-regulation in tumor patients
Passive antibody therapy
Using monoclonal antibodies to treat tumors
Characteristics of monoclonal antibodies to treat tumors
1) mAb to TAA that activates complement and leads to cell lysis/ADCC
2) mAb tagged with poison that destroys tumor
3) mAb to growth factors to inhib self-stim tumors
Antibody/T cell therapy
2 coupled mAb (one against CD19 and one against CD3) binding T cells to B cell lymphoma cells to facilitate T cell destruction
How does BCG treatment cause tumor regression? (1)
BCG = TB vaccine
1) Increases RE activity to incr production of macrophages to clear blocking factors from tumors cells --> incr immune ability to clear tumor cells
How does BCG treatment cause tumor regression? (2)
Inject BCG into tumor causes delayed hypersensitivity reaction that kills tumors (melanoma/superficial bladder carcinoma)
Adv/Disadv with monoclonal antibodies to treat cancer
Adv: selective to target TAA and growth factors of tumor cells
Disadv: Very expensive to develop and produce