082514 tumor immunity Flashcards
why does immune response usually fail to prevent tumor growth?
imm system wants to prevent self-reactivity so there are things to prevent immune reactivity to cancer (immune system can control immunogenecity against tumor)
the most important cells for response to cancer
T cells and APCs
Is CD8 T cell recognition of tumor antigens presented on cancer cells on MHC class I effective?
No, because the CD8 cells cannot be directly activated by the tumor cells, which lack second co-stimulatory molecules
the CD8 cells would need professional APCs to cross present phagocytosed tumor cells on MHC class I to become activated (b/c APCs provide costimulator)
what kinds of tumor antigens are recognized by immune system?
mutated self protein
product of oncogene or mutated tumor suppressor gene
overexpressed or aberrantly expressed self protein
oncogenic virus antigen
after T cell activation by APC presenting tumor antigen, how do T cells kill tumor cell?
pre-activated T cells in this manner no longer need co-stimulatory signal and can kill tumor cell
what T cells need costimulatory signals on APC to become activated?
CD4 and CD8
cytolytic T lymphocytes
activated CD8 T cells
barriers to cancer immunity
expansion and recruitment of regulatory cells
secretion of immunosuppressive cytokines
activation of negative regulatory pathways (cancer cells can express ligands for negative signaling proteins on T cells)
evasion of immune recognition
how to manipulate immune response to cancer?
interfere with immune suppression
over-stimulate immunity
3 approaches in cancer immunotherapy
monoclonal antibodies
adoptive cellular immunotherapy
vaccines
monoclonal antibodies provide immunotherapy against cancer how?
kill tumor cells by cellular or non-cellular mechanisms
ex of non-cellular: complement, toxin, block survival signal by binding receptor on tumor cell, provide pro-apoptotic signal to activate receptors on tumor cell
other than tumor cells, where else potentially can monoclonal Ig target for immunotherapy against cancer?
potentially tumor associated blood vessels, growth factors, tumor associated stroma
immune checkpoints
inhibitory pathways (receptor and ligand) on the immune system to maintain sel-ftolerance
cancers can take advantage of these pathways
ex of monoclonal Ig interfering with immune suppression for cancer therapy
CTLA4 blocking antibody
PD-1 blocking antibody
negative aspect of treating with monoclonal Ig that is the CTLA4 blocking antibody
triggers autoimmunity
