BASICS OF TUMOUR IMMUNOLOGY

How does the APC Bind to T cell

• PD-1 (T cell) – PD-L1 (tumour cell): Inhibits T-cell activity. ✓

• CTLA-4 (T cell) – B7/CD80/CD86 (APC): Inhibits T-cell activation. ✓

• CD28 (T cell) – B7/CD80/CD86 (APC): Costimulation. ✓

What does specific tumour rejection in mouse models indicate/ Foundation of tumour vaccine

It shows the foundation of tumour vaccine. Once antibodies are formed against the irradiated tumour, when exposing viable cells of the same tumour, memory cells are activated and can still destroy the tumour. On the other hand, exposing viable cells of the different tumour can cause tumour growth because the immune cells does not recognize this.

Lymphoid cells gives rise to? Myeloid gives rise to?

Lymphoid cells – B T NK

Myeloid – DC, Macrophage, Leukocytes

Intracellular/Extracellular AG uses which MHC

Intracellular AG – MHC 1

Extracellular AG – MHC 2

In each stage (except 4) what inhibition/therapy is ideal

Which picture corresponds to what MHC and CD4

left- MHC 1 . Right MHC 2

How does dendritic cell get naive T cell fully activated? What are the 3 stimulatory factors involved?

Costimulation

1. MHC + Peptide on APC

2. B7 (CD80/CD86) on APC → CD28 on T cell

3. T cell differentiation by cytokines

Which TH cell differentiation is helpful with tumour environment

TH1

Role of mature and immature DC and When does immature become mature

Role of immature DC – Collect antigen

Role of mature DC – T cell activator

When it receives inflammatory or danger signals

What are toll like receptos (TLR)

Why can a TLR agonist be used as an adjuvant to tumour vaccines?

Pattern recognition receptors: They detect conserved molecular patterns associated with microbes and/or danger and hence activate APC.

 

Tumour vaccine helps dendritic cell identify an antigen and take it up. TLR helps in maturing of DC by increasing the receptiveness to danger signals. Mature dc can cause t cell activation. So in a way it corresponds to the co-stimulation

What is STING pathway? What does it detect? Trace the pathway

Danger-sensing pathway;

detect DNA where it shouldn't be: in the cytoplasm

Cytosolic DNA → cGAS → cGAMP → STING → TBK1 → IRF3 → IFN-I

Cytosolic DNA → cGAS → cGAMP → STING → NF-κB → inflammatory cytokines

Why dendritic cells are used in cancer vaccines

→ capture tumor antigen

→ process it

→ present it on MHC

→ provide co-stimulation

→ produce instructive cytokines

→ activate tumor-specific T cells

Name 3 antigens T cell recognise

Neoantigens

Viral antigens

Overexpressed antigens

How is a car T different from a regular TCR. How is it helpful in adoptive cell transfer

Normal TCR:

Recognizes peptide presented by MHC

CAR:

Recognizes a surface antigen directly

Adoptive cell transfer- active or passive therapy? Name 2 types of it

TIL and CAR-T

Example of prophylactic + active immunotherapy

HPV Vaccine