Avoiding Immune Detection Nov 28, 2017

Hallmarks of Cancer, 2011

Immune Cell Function in Cancer

Immune Cells Adaptive Immunity Innate Immunity

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

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

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

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

B Cell Activation Antigen = protein, lipid, or polysaccharide

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

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

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

Cancer Immunity Cycle

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

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

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