11 cancer immunotherapy Flashcards
What was the outcome of using heat-killed streptococcus? - william coley
It became widely used but was made illegal by the FDA in 1962.
What are key mechanisms of immune evasion?
Downregulation of MHC molecules, expression of immune checkpoint ligands, and recruitment of immunosuppressive cells.
How does chemotherapy activate the immune system?
By activating T cells and NK cells.
What is Immunogenic Cell Death (ICD)?
A type of cell death that triggers an immune response against cancer cells.
What is a drawback of chemotherapy in immune activation?
It is not immune-specific and can be difficult to tolerate.
What presents tumour antigens to T cells?
MHC molecules on antigen-presenting cells (APCs).
How do T cells become tumour-specific?
hey clonally expand and express TCRs specific for tumour antigens.
What do T cells release to kill tumour cells?
Cytolytic enzymes such as granzyme and perforin.
What are immune checkpoints?
Ligand-receptor pairings that regulate immune responses.
Which cells typically express immune checkpoints?
Primarily T cells, but also tumour cells and other immune cells.
How do tumour immune checkpoints affect CD8 T cells?
They suppress CD8 T cell activity, allowing tumour cells to evade immune attack.
They suppress CD8 T cell activity, allowing tumour cells to evade immune attack.
Co-stimulatory CD80-CD28 signalling.
What does TCR signalling induce?
T cell proliferation, cytokine production (e.g., IFN-γ), and cytotoxic enzyme expression.
What is the role of PD-L1-PD1 signalling?
It prevents excessive immune activation but can also inhibit tumour immunity.
What happens when the PD-1 gene is deleted in mice?
hey develop autoimmune disease.
What does antibody-mediated ICB do?
Blocks immune checkpoints to restore T cell function against tumours.
Name an FDA-approved anti-PD-1 therapy.
Nivolumab or Pembrolizumab.
What is Ipilimumab’s target?
CTLA-4, a checkpoint protein that downregulates T cell activity.
What is the main limitation of ICB therapies?
Not all patients respond, and responses can be short-lived.
Why do some tumours not respond to ICB therapy?
Tumours may lack tumour-infiltrating lymphocytes (TILs) or contain immunosuppressive cells like Tregs and MDSCs.
How can the effectiveness of ICB be improved?
By combining it with chemotherapy, radiotherapy, or drugs targeting immune suppressor cells.
What is a strategy to reprogram the tumour immune microenvironment?
argeting immune-suppressive cells like neutrophils.
ow do neutrophils correlate with cancer progression?
They are associated with disease stage and prognosis in hepatocellular carcinoma (HCC).
What phenotype do neutrophils in HCC have?
An immunosuppressive phenotype.
: What is a potential way to manipulate neutrophils for cancer treatment?
Targeting their chemokine receptors, such as CXCR2.
What existing drugs could be repurposed to target neutrophils?
CXCR2 inhibitors, already used in lung disease.
What carcinogen is used to induce liver cancer in mice?
Diethylnitrosamine.
What dietary background mimics fatty liver disease?
The ALIOS diet.
What treatment groups were used in the study?
Vehicle control, anti-PD-1 alone, CXCR2 inhibitor alone, and anti-PD-1 + CXCR2 inhibitor.
What was the effect of CXCR2 inhibition?
It extended overall survival (OS) in immunotherapy.
How did CXCR2 inhibition affect the tumour microenvironment?
It reprogrammed tumour-associated neutrophils and altered tumour transcriptomes.
What is CAR-T therapy?
A therapy where patient-derived T cells are engineered to express tumour-specific TCRs.
What type of cancer has CAR-T therapy been most successful in?
Blood cancers.
What are barriers to CAR-T therapy in solid tumours?
Poor migration, tumour extracellular matrix, CAR-T exhaustion, and immune suppression.
What is a key toxicity concern in CAR-T therapy?
Severe immune-related toxicities, even in successful cases.
ow does an mRNA vaccine for cancer work?
It uses tumour samples to create personalised vaccines based on tumour mutations.
What is the goal of personalised cancer vaccines (PVC)?
To prevent cancer recurrence after surgery.
What is a recent trial result for PVC in kidney cancer?
All 9 patients remained cancer-free at 40 months.
hat is the function of ICB therapy?
Blocking PD-1/PD-L1 or other immune checkpoints to enhance T cell function.
How does CAR-T therapy differ from ICB?
CAR-T is personalised to attack specific tumours, while ICB broadly enhances T cell activity.
