L18 - Tumour immunology and immunotherapy Flashcards
An overview of immune response/basic immunology. Immune response to cancer. Tumour antigens and their identification. Contents: - How manipulation of immune system can help in treatment of cancer? - Types of tumour antigens that can be targeted. - Activation of anti-tumour T cells by immunisation with cancer antigens. Adoptive transfer. - To identify mechanisms that limit cancer regression despite the presence of anti-tumour T cells? - Strategies of tumour immune evasion.
What are the effectors of the immune system?
Cells - (monocyte/macrophage, NK & CTLs)
Antibodies
Complement
What four cell types are effectors of innate immunity?
Neutrophils - phagocytosis
Macrophages - phagocytosis & professional antigen presentation
Dendritic cells - Professional antigen presentation, costimulatory signals/cytokines
Natural killer cell - Lysis of viral-infected cells, costim/activation of macrophages.
What are the triggers of the innate immune response?
Bacterial cell wall components. PAMPS recognised by PRRs.
Give an example of a PRR
TLR4 (4)
What are the two arms of the adaptive immune response?
Humoural (B cells)
Cell mediated (T cells)
What three interactions are important in T cell activation by APC?
Signal 1 is T-cell receptor - MHC-antigen recognition.
Signal 2 is costimulatory molecules such as CD28 - B7
Signal 3 is relevant cytokines
What is the evidence that there are immune responses to tumours?
Infiltration of lymphocytes and macrophages are associated with better prognosis.
Peripheral blood NK activity correlates with survival.
Peripheral lymphocyte count falls as cancer overwhelms host.
Non-specific vaccines can stimulate macrophage, improves prognosis.
Higher incidence of tumours in immunosuppressed individuals.
What role does T cell infiltration play on bladder cancer prognosis?
Positive correlation with survival.
What have we learned from cancer cells using inbred mice?
Tumour cells are distinguishable from normal cells immunologically.
Presence of tumour specific antigen.
Means vaccination against cancer is possible.
What is the ideal tumour antigen?
Expressed uniquely on cancer cells.
Be necessary for transformation of normal cells into cancer cells or essential for survival.
Be immunigenic.
What are the three kinds of tumour antigen?
Tumour-specific transplantation antigens (TSTAs)
- Unique to tumour cells.
- May arrise due to mutation
- Presented on MHC-I
Tumour-associated transplantation antigens (TATAs)
-Proteins expressed on normal cells.
inappropriate expression of embryonic gene or overexpression of normal protein.
Virus antigens
oncogenic virus antigen
What three tumour-related methods can tumours evade the immune system?
Failure to provide target (lack of MHC or epitope)
Failure to induce immune response
Regulating immune response (activating T regs)
What are three host-related ways tumours can escape immune system?
Immunosuppression.
Deficiency in APCs.
Failure to infiltrate tumour
What occurs to MHC-I (HLA class I) in high-grade prostate cancers?
Exhibit different degrees of loss.
May be due to complete loss innapropriately can cause NK-induced death
Can poorly or undefined antigens be used in vaccination?
Yes, whole cell vaccine.
mixture of 3 sublethally irradiated allogenic maloma lines, with different HLA haplotypes can be used in vaccine.
lysate can also be isolated and used from this process.
the transcriptome (total RNA) of tumour cells can be loaded onto dendritic cells too
What are some approaches to identify new tumour antigen?
(potential to be Jan. exam question)
Check onenote for details. Read articles for exam.
- Genetic approach - transfecting cDNA libraries from tumour cells into target cells (matched MHC) used CTL.
- Biochemical approach - peptide eluted from tumour cells (or MHC) and purified for sequencing.
- Reverse immunology - in vitro sensitisation used to generate T cells that are reactive against specific Ag.
- Proteomics, cancer patients sera in 2D western blot using autoantibodies. Immunoreactive target protein are identified by mass spectrometry.
- Identification of tumour antigens by SEREX (serologic analysis of recombinant cDNA expression libraries).
