Tumor immunology

zijimubo1's version from 2016-12-15 17:20

Tumor immunology

Question Answer
What is tumor immunology?Tumors express Novel antigens that are not expressed on normal cells or they are expressed on normal cells at low levels.
What is immune surveillance?Ability for immune system to perceive, respond to, control growth and metastasis of neoplasms.
What is immune editing?Three stage of tumor development: elimination, equilibrium, escape
What is elimination phase in tumor development?Eradication of neoplasm, either complete or leave residuals.
What is equilibrium phase in tumor development?Remaining tumor residuals enter a dormant state of no growth or metastasis.
What is escape phase in tumor development?Immune surveillance fails and tumor progression proceeds.
Innate elements in tumor elimination and equilibrium.NK cells, neutrophils, macrophages
Adaptive elements in tumor elimination and equilibrium.CD8+ T cells and CD4+ T cells
Immune elements involved in escape phase.T-reg that suppress T cells and NK cells
What are MDSC?myeloid-derived suppressive cells; express CD11, CD34, CD45; High levels in metastasis

Tumor antigens

Question Answer
Oncofetal antigensexpressed in embyrogenesis but disappear in adults.
Carbohydrate antigensexpressed in low levels in normal tissues, but over expressed on some tumors
Clonal or differentiation antigens on lymphomasmonoclonal B cell lymphomas express surface immunogloblulins Ig's with the same idiotype.
Mutant cellular gene productsgrowth factor recpetors (EGFR)
Viral gene productstumors induced by viruses express tumor-specfic antigens (ex. Epstein Barr virus - nasopharyngeal carcinoma)
CEAcarcinoembryonic antigens - expressed in colon and pancreatic cancers
AFPalpha-fetoprotein - increases in pregnancy, decreases after partition ; liver and colon cancers
Gangliosidesglycolipid found in neurons, overexpressed in melanoma and colon cancers
Mucinsunder-glycosylated mucin that doesn't require MHC for T-cell recognition. Breast, ovarian, pancreatic cancers.

Host response to tumors

Question Answer
Lymphocyte the kills cells without self MHC INK cell
Kills cells by perforin-induced osmotic lysisNK cell
TNF alpha induced apoptosisNK cells and Macrophages
FasL-induced apoptosisNK cell
ADCC (antibody-dependent cellular cytotoxicity)NK cell
Expresses CD16 (Fc-gammaR)NK cell
Display anti-tumor propertiesM1 macrophage
Display pro-tumor immunosuppressive propertiesM2 macrophage
Release ROSM1 macrophage
Produces antibodiesB cell
Can promote ADCC and complement through antibodiesB cell
Produces IFN-gamma to activate NK cells and MacrophagesT cell
Produce long-term arrest of tumor growth through IFN-gamma and TNF-alphaT cell
Produces angiogenic factorsM2 macrophage
Stimulate by IL-4, IL-13, IL-10, GlucocorticoidsM2 macrophages
Releases IL-12 and TNF-alphaM1 macrophage
Promotes Th1 responseM1 macrophage
Release VEGF, MMP, IL-10, and arginase 1M2 macrophage
Promotes Th2 responseM2 macrophage

Tumor escape

Question Answer
Reduce expression of tumor-specific and MHC antigensCTLs bind to MHC Class I and kill tumor cells; Tumors downregulate expression of antigen signals
Cell membrane expression of apoptsis-induced moleculesFasL and Programmed Death Ligand-1 (PD-L1) express on tumor cells (melanomas) to inhibit T cell proliferation and induce T-cell apoptosis
Immunosuppresive and anti-inflammatory moleculesTGF-beta, IL - 10 , indoleamine (IDO) suppress immune responses locally
Immunosuppresive and anti-inflammatory cellsTreg cells and Myeloid-derived suppresor cells(MDSC) suppress NK cells and T-cell death
Immunosuppresive and anti-inflammatory inhibtor Soluble FasL releases and binds to Fas, blocking Fas-FasL surface interaction
Inactivation of complement cascadeComplement regulatory proteins (CRP); expressed by tumors on surface to inactivate complement and complement antibodies
Myeloid Derived-Suppresive Cells (MDSC) - supress NK cell, T-cell; Promote angiogenesis; Produce ROS to T-cell receptors;

Tumor drugs

Question Answer
Rituximabanti-CD20; CD20 expressed on B-cells; CLL; Modest efficacy; ADCC????
Trastuzumabantibody to Her2; Her2 overexpressed in breast cancer; Her2 associated with proliferation and angiogenesis; inhibits angiogenesis + ADCC
Bevacizumabantbody to VEGF; 1st line Colon cancer; Inhibits angiogensis
Ipilimumabanti-CTLA4; 1st and 2nd line Melanoma; unique kinetics requiring months/yrs for regression; Blocks CTLA-4 "removes breaks" in lymph nodes promoting T cell proliferation
NivolumabAnti-PD-1; immune checkpoint antibody; PD-1/PD-1L interactions inhibit T cell