increased cellular proliferationROS and cytokines released from neutrophils cause DNA damagedevelopment of pro-metastatic niche
cancer from chronic inflammation
Infiltration of tumour promoting fibroblasts, and suppressive macrophages and myeloid-derived suppressor cells
what is a pro-metastatic niche
lose MHC-1 expression
how can tumours evade immune system
immunosuppressants suppress T and NK cellsincidence of viral and spontaneous cancer higher in immunosuppressed
cancer in transplant patients
over expressed self antigens from dysregulated gene expressionalso by normal cells in low levelseg PSA
what are tumour associated antigens (TAAs)
neo-antigens that are tumour specific, result from mutationseg BRCA1/2
what are tumour specific antigens (TSAs)
release a lot of tumour antigens TAAs on death to reawaken immune system
how are dying tumour cells immunogenic
kills tumour cells so they release antigen also chemo can kill MDSC and niche
how does chemo awaken the immune system
vaccinescheckpoint inhibitorsCAR T cells
cancer immunotherapy types
T cells can lose interest in attacking cancer due to excess cancer antigens in the blood or the tumour microenvironment and become exhausted. Need to block molecules that induce T cell exhaustion eg CTLA-4/PD1
how do immune checkpoint inhibitors work
initially made in mice but made so they do not cause an immune response
what does humanized antibodies mean
patients T cells are transduced using retrovirus containing chimeric antigen receptor specific to cancerpreconditioning chemo used to ablate other T cells so CAR T ones will proliferatemodified T cells injected back into patient
how does CAR T cell therapy work
anti CD19 for B cell tumours
examples of CAR T cell therapy
all normal B cells ablated by chemo, CAR T cells kill malignant ones. pt now needs done infusions of gamma globulins
what happens after CAR T cell therapy for B cell malignancies
cytokine storm due to release of IL-6 from macrophages. need to administer steroids and anti IL6
what can serious side effect can occur after CAR T cell therapy
A
Tumor-associated macrophages and fibroblasts: (A) contribute to cancer progression(B) activate the immune response to cancer(C) outcompete tumours for the pre-metastatic niche (D) produce antibodies that destroy tumour tissue
D
A common form of immune evasion in cancer is the: (A) release of IL-1 and TNF-a (B) activation of pro-apoptotic pathways (C) migration away from attacking T cells (D) downregulation of MHC-I
B
The solid tumour microenvironment is mainly composed of (choose the best answer): (A) cancer cells only (B) cancer cells, MDSC, fibroblasts & macrophages (C) fibroblasts & macrophages (D) hyperoxygenated tissue at physiological pH
B
MDSC: (A) participate in the anti-cancer immune response (B) suppress the immune response to cancer (C) are fibroblasts that wall off the tumour (D) are cancer stem cells
C
Tumour antigens that are the result of mutations are: (A) tumour-associated antigens (TAA) (B) unlikely to contribute to tumour immunity (C) neoantigens or tumour specific antigens (TSA) (D) a group of antigens that include prostate specific antigen
A
Prostate specific antigen (PSA) is: (A) a tumour associated antigen (TAA) (B) a neoantigen or tumour specific antigen (TSA) (C) often mutated in prostate cancer (D) absent from the circulation of unaffected individuals
B
Anti-PD1 and anti-CTLA-4 are classed as immunotherapeutics because: (A) they suppress cancer genomic instability (B) they are monoclonal antibodies that activate the immune response to cancer (C) they suppress the immune response (D) immunology is just so damn fashionable these days
C
A TIL is a: (A) Taphephobia Inducing Lycopene (B) Tenesmic Idiopathic Lipoma (C) Tumour Infiltrating Lymphocyte (D) Teratoma Infiltrating Lymphoma
E
What is the likely effect of chemotherapy and radiation on the immune response to cancer? (A) Immunogenic cell death of tumour cells (B) Depletion of MDSC (C) Immune suppression (D) Neutrophil death (E) All of the above may occur
D
CAR therapy can result in a 'cytokine release syndrome (CRS)' a severe febrile reaction. An effective treatment that was chanced upon for Emily Whitehead's CRS (and saved her life) was: (A) Imiquimod (B) anti-PD-1 and anti-CTLA-4 (C) TIL therapy (D) anti-IL6 receptor (tocilizumab) - a drug used in rheumatoid arthritis
D
The receptors in CAR T cells are composed of: (A) T cell receptors (TCR) (B) NK cell receptors (C) T cell receptor and intracellular B cell receptor components (D) antibody sequences and T cell signalling motifs
D
Transplant patients have a higher risk of certain cancers because: (A) transplants often carry infectious diseases (B) systemic inflammation is common following transplantation (C) immunosuppressive drugs cause inflammation (D) immunosuppressive drugs weaken the immune response
D
Prior to their introduction into the clinic, mouse monoclonal antibodies (mAb) are humanised to: (A) prevent murine auricular promorphism (MAP) syndrome (B) decrease circulating half-life (C) prevent mouse sequences from attacking our body (D) minimise immune reactions to mAb sequences