1. Avoiding Immune Detection
Nov 28, 2017

2. Hallmarks of Cancer, 2011

3. Immune Cell Function in Cancer

4. Immune Cells
Adaptive Immunity
Innate Immunity

5. Types of Immunity Innate Immunity
-Respond early and non-specifically to infection
-Neutrophils, eosinophils, basophils, dendritic cells, natural killer cells, macrophages
2. Adaptive Immunity
-Respond later during infection
-Respond specifically to antigens presented by antigen-presenting cells
-B cells, T cells

6. Immune System’s Role in Cancer
Anti-Tumor Effects
Pro-Tumor Effects
The immune system is influenced by the tumor, and the tumor is affected by the immune system

7. Cells of the Adaptive Response
B cells
-Functions to synthesize and secrete antibodies
-Antibodies can recognize almost any antigen encountered by the immune system
-Once recognized, they can coordinate cell-mediated cell lysis
-Known as humoral immunity
T cells
-Maturation occurs in the thymus
-2 types
-CD4+ helper T cells
-CD8+ effector T cells
-Contain T-cell receptors that recognize antigen presented to them via antigen-presenting cells
-Known as cell-mediated immunity

8. Antibody Composed of: -2 identical heavy chains
-2 identical light chains
-Joined by disulfide bonds
-Contains an antigen-binding domain
-Variable region, Fab
-Binds antigen
-Constant region, Fc
-Regulates the immune response

9. B Cell Activation
Antigen = protein, lipid, or polysaccharide

10. T Cells
-Coordinate the immune response and eliminate virally infected cells and tumor cells
-Long-lived memory Tc ells are also producing allowing a faster, stronger response to antigen re-exposure
-Secreted molecules of B and T cells include:
-Cytokines
-Interferon-γ
-Interleukins
-Chemokines

12. Tumor Suppressive Roles
The immune system protects against cancer:
Protects against viral and bacterial infection (causative agent of some cancers)
Resolves inflammation (promoter of cancer)
Recognize and kill tumor cells (immunosurveillance)
-In mice lacking Interferon-γ or adaptive immunity were more susceptible to cancer
-In humans on immunosuppressive drugs has a higher incidence of cancer
The Immune system can act as a tumor-suppressive defense

13. Cancer Immunity Cycle Release of cancer cell antigens
Presentation of cancer antigens on antigen-presenting cells
Priming and activation of T cell in lymph nodes
Transport to tumors via the bloodstream
Infiltration of T cells into tumors
Recognition of cancer cells
Tumor cell death

14. Cancer Immunity Cycle

15. Cancer Cell Antigens -Tumor-specific antigens:
-Molecules that are unique to cancer cells
-Mutant p53 peptides
-Molecules that are differentially expressed
-HER2 overexpression
-Released by dying cells picked up by the major histocompatibility complex on antigen-presenting cells

16. Cancer Cell Antigens -T Cell Receptor recognizes the antigen
-MHC-antigen-TCR interaction triggers T cell activation, called T-cell priming

17. T Cell Activation
-T cells then infiltrate the tumor, recognize, and bind tumor cells
-When fully activated, they release molecules, perforin and granzymes, and express ligands for death receptors
-The Cancer Immunity Cycle does not operate optimally in cancer patients
-The tumor microenvironment is a source of immunosuppression