Tumor Immunology Flashcards
Cause of Cancer
Accumulated mutations in genes that ocntrol cell growth and death
What do carcinogens do?
Induce mutations into DNA
T or F. Typically a single genetic abnormality will lead to cancer.
F. Accumulations of mutations tend to lead to cancer cell development
Why are some individuals more prone to develop cancer (even with comparable lifestyles to others)
Inherited mutations in genes that control DNA stability or growth (Ex. BRCA1, BRCA2)
Size of average tumor when first visible on Xray?
At death of patient?
10^8
10^12
Describe characteristics of a malignant tumor
Malignant cells are more aggressive in growth
Spread to nearby tissues/different organs through lymph and BV
What is a carcinoma?
Epithelial Cell Tumor
What is a leukemia?
Tumors of circulating cells
What is a lymphoma?
Solid tumor in lymph node
What is a myeloma?
Tumor of Bone marrow cells
What is a sarcoma?
Tumor of Connective Tissue Cells
Viruses associated with human cancers?
Papillomavirus (Uterine Cervix)
Hepatitis B Virus (Liver Cancer)
Epstein Barr Virus (Burkitt's Lymphoma, B-Cell
Lymphoproliferative disease)
HTLV-1 (Adult T-cell Leukemia)
HIV-1 (Kaposi's Sarcoma)How might viruses induce proliferation?
Blocking P53 and Rb
Can tumor cells grow in another person?
Usually, No.
Yes if the other person is the same MHC haplotype
Four immune cells responsible for finding tumors
CD4, CD8, NK cells, and B cells
What do T and B cells target in cancer?
Tumor antigens that are differentially expressed by tumor cells and normal cells
What are tumor specific antigens?
Mutant peptide presented in cancer cells that is distinct from normal healthy cells
What are tumor-associated antigens?
- Antigens brought about by reactivation of embryonic genes
2. 10X or more overexpression of self proteins
Give an important example of a tumor-specific shared antigen
Melanoma antigen - 1
Found on melanomas and other transformed cells
Give an important example of a tissue-specific antigen found on normal and transformed cells.
Tyrosinase
Give two examples of Oncofetal antigens
Carcinoembryonic Antigen (CEA) -- Colon Cancer Alpha-fetoprotein -- Liver and testis cancer
Give two examples of differentiation antigens
Common acute lymphoblastic leukemia antigen (CALLA/CD10) – Acute Lymphoblastic Leukemia
PSA – Prostate Cancer
Give an example of abnormal post-translational modification leading to cancer
Underglycosylation of Mucin caused by MUC-1 – Breast and Pancreas
Give an example of a cancer with a mutated oncogene or tumor suppressor antigen.
Cyclin-dependent kinase 4 – Melanoma
MART2. Name the disease, HLA restriction.
Melanoma. A1
ME1. Name the disease, HLA restriction.
Non-small cell lung carcinoma. A2
p53. Name the disease, HLA restriction.
Head and Neck Squamous Cell Carcinoma
A2
KIA0205. Name the disease, HLA restriction.
Bladder
B44
Trisephosphate isomerase. Name the disease, HLA restriction.
Melanoma
DR1
BCR-ABL Fusion Protein. Name the disease, HLA restriction.
CML
DR4, B8, A2
Five cells involved in cell mediated tumor response..
What do they do?
CD4 -- Control other cells by cytokines CD8 -- direct lysis NK cells -- direct lysis gd T cells -- cytokines and lysis Eosinophils -- Degranulation
Two important roles of Antibodies in tumoral response?
Facilitate NK cell mediated lysis of tumor cells
Activate complement reaction
How does the body deal with tumors that lack MHC1 expression?
NK cells kill them
How do dendritic cells present to both CD4 and CD8 T cells?
Dying tumor cell is taken in by both endocytosis and membrane fusion
Give six methods Tumors can use to evade immune response
- Outgrowth of antigen-negative variants
- Loss/Reduction of MHC proteins
- Secretion of Immunosuppressive cytokines
- Induction of CTL apoptosis via FAS ligand
- Lack of Co-stimulatory signals
- Soluble tumor antigens (to induce tolerance)
How common is removal of MHC 1 expression
30-50% of tumors
Examples of immuno suppressive cytokines that might be secreted by tumors
TGF-beta TH2 cytokines (IL10)
How might tumor cells that ditch their MHC1 continue to evade NK Cells?
Shedding of MHC Class I related Chain (MIC), a ligand of NKG2D (NK activating receptor)
Describe MIC in tumor biology.
Normally elevated expression in tumor cells.
NKG2D on T cells and T cells bind it –> Kill Tumor
By cleaving MIC from surface, soluble can bind lymphocytes and not involve the tumor
Tumor can now survive and proliferate
Actions of TGF-beta that support tumor growth?
Induce Tregs (inhibit CTL, release more TGF and IL-10)
Inhibit CTL
Inhibit TH1
Five types of immunotherapy
Non-specific stimulation Active Immunization with tumor antigens Cytokine therapy Adoptive cellular monotherapy Anti-tumor antibodies (coupled to cytotoxins/radioiso)
Example of Non-specific adjuvant therapy.
Injecting killed mycobacterium (BCG) into bladder to treat superficial bladder cancer
How might non-specific adjuvant therapy work?
Bacterial products increase T cell Response
Induce co-stimulation molecules and MHC molecules of APCs
How can antibodies against tumor antigens be used?
Immunotoxins and induction of ADCC by NK cells
Explain what is meant by tumor vaccines.
Tumors taken at surgery are manipulated ex vivo – used as vaccine. Made to express B7, GM-CSF, or IL12 in tumor cell
Also…tumor antigens can be used (ex. CEA)
What is dendritic cell therapy?
Patient Dendritic cells are isolated and loaded with tumor antigen in vitro. Cells are injected into patients to boost anti-tumor T cell response
What happens in T cell therapy?
Patients T cells are activated in vitro with tumor antigens and cytokines, inject back into patients
What is Sipuleucel-T/Provenge?
A cancer vaccine for prostate cancer
Patient Blood->DC + Fusion protein with PAP and GM-CSF-> infusion into patient
Explain monoclonal antibody treatment with Rituxan
Anti-CD20 antibodies to target non-Hodgkin’s lymphoma
Name two types of radiolabeled antibodies used to detect cancer
Oncoscint – Colorectal + Ovarian
Prostascint – Prostate
Explain how antigen-GM-CSF fusion proteins work?
Patient Monocytes are cultured with fusion protein of GM-CSF and PAP
Induces DC development, PAP presented on MHCII
Activated cells infused into patient, present to T cells
How does Anti-CTLA4 antibody work in cancer treatment?
If B7 binds CD28, activation
If B7 binds CTLA4, anergy
Antibody blocks CTLA4, so any TCR binding will result in activation
Explain chimeric antigen receptor-transduced T cells
Chimeric receptor is added to T cells by R-Trans activity
T cells can now bind with Ab domain
T cell killing power with B cell targeting skills
