Please enable JavaScript.
Coggle requires JavaScript to display documents.
CANCER IMMUNOLOGY L23 Part I (IMMUNE RESPONSES TO TUMORS (EVASION OF…
CANCER IMMUNOLOGY
L23 Part I
Mutations involving
Proto-oncogene :arrow_right: oncogne
Tumor supressor gene
DNA repair gene
TUMOR ANTIGENS
TUMOR SPECIFIC ANTIGEN
TSA
Mutated non-tumorigenic self-proteins
(passenger mutations DO NOT CONTRIBUTE to tumor growth, but can use to ID)
Can be recognized as foreign by immune system
Products of oncogenes
(Philadelphia chrom [bcr-abl Tyrosine Kinase constitutively active causes CML)
Imatinib (Gleevec) = Bcr-Abl tyrosine kinase inhibitor blocks tumor proliferation;
targeted therapy
Products of mutated tumor suppressor genes
EX: mutations in p53
(normally stops cell cycle to allow DNA repair or cell apoptosis)
Antigens from oncogenic viruses
(elicit anti-tumor T-cell responses)
EX: HPV antigens
E6 (p53) & E7 (Rb); if non-func can cause cancer
Gardasil
(2, 4, or 9 HPV strains that self-assemble to form virus-like particles; induces protective immunity against infection & cervical cancer
TUMOR ASSOCIATED ANTIGEN
TAA
Overexpressed self-proteins
(normal cell proteins, overexpressed in tumors)
EX: Her2/neu receptor (EGF) overexpressed in breast cancers
Pertuzamab (Perjeta) & Transtuzumab (Herceptin)
(mabs that bind to Her2/neu preventing receptor dimerization & downstream signaling)
Aberrantly expressed self-proteins
(normal cell proteins expressed in embryonic dev; typically off in adults
EX: Carcinoembryonic Antigen (CEA) for epithelial tissue
(glycopro adhesion molecule in gut formation; increased in many carcinomas
IMMUNE RESPONSES TO TUMORS
Tumor-specific CTLs
MOST IMP RESPONSE against tumors
:explode:
CD8 = Cytotoxic T Cells
CROSS PRESENTATION
cDCs present antigen to CTLs in secondary lymphatics; CTLs go to site and kill tumor
cDCs can also present to
Helper T cells
:explode:
CD4
Antibodies
(enhance innate immunity: opsinization, complement, ADCC)
NK cells
(FIRST LINE OF DEFENSE; effective against tumors with :arrow_down: Class I MHC
Macrophages
(INF-gamma activates;
secrete TNF; APC for T cells
#
#
EVASION OF IMMUNE RESPONSE
(immune resp to tumors impart selective pressure resulting in survival and growth of tumor
:arrow_down:
immunogenicity
Antigenic Modulation/Loss
(loose CTL antigens or mutations inhibit antigen recognition)
Tumor cell secretion/expression of immunosuppressive molecules
Tumor ligand binds T cell inhib receptor
Secrete immunosuppresive cytokines
:star:TGF-B, IL-10, IDO
Inhibit T cell response
Promote Treg cell recruitment
:arrow_down:MHC Class I expression
T cell can't recognize