LT14 - Cancer immunity and immunotherapy

Question 1

When has cancer a good prognisis?

Answer 1

• When there are T-cells present (CD4+ T-cells)
• When tertiary lymphoid structures present
• When there are M1 marcophages present, want die zijn pro-inflammatory

Question 2

When has cancer a bad prognisis?

Answer 2

• When there are Treg cells present
• When there are M2 macrophages present
  these are both immune suppresive

Question 3

Which proteins are being exprepssed to T-cells by tumor cells?

Answer 3

• Self proteins (if you trigger immune responses you coukd get severe side effects)
• non self proteins

Question 4

Different self proteins

Answer 4

• overexpressed antigens
• Cancer testis antigens
• oncofetsal proteins

Question 5

Different non self proteins

Answer 5

• Neo-antigens: derived from somatic mutations

- Viral-antigens: produces by virusses

Question 6

Cancer immunity cycle =

Answer 6

Tumor cells die –> release tumor cells antigens –> picked up by APC’s (dendritic cells) –> travel to secondary lymphoid structures –> present the antiogen to T-cells –> T-cells infiltrate the tumor tissue –> T-cells kill the cancer cells

Question 7

What produces CD8+ T-cells which perforates the target –> apoptosis

Answer 7

Protesases like perforin and granzyme

Question 8

What happens when Fas on the tumorcell binds to the Fas ligand on T-cells?

Answer 8

Apoptosis

Question 9

Th1 type

Answer 9

• CD4+ T-cells that can produce IL-2 and IFN gamma –> supports T-cells and APC
• Pro-inflammatory, so good prognosis

Question 10

Th2 type

Answer 10

• Treg cells that produce TGF-beta and IL-10

- bad prognosis

Question 11

forms of immune escape

Answer 11

• HLA/MHC class 1 loss (tumors can’t reccognize tumor antigens anymore)
• PD-L1 expression in tumors (PD-L1 is a ligand and can bind to T-cells and ginves negative feedback
• Immune suppressed microenvironment (due to TGF beta)

Question 12

Which has a better prognose?

1. Polymerase deficient cells and MMR deficient cells
2. DNA replication repair preoficient cells

Answer 12

1

Question 13

IL-2 therapy

Answer 13

• Pro-inflammatory

- for melanoma’s and metastatic renal cell carcinoma

Question 14

TIL-therapy

Answer 14

• Take the tumor out of the patient and put it back with IL-2 in it
• Specific, but lots of work

Question 15

Antigen therap - viral proteins

Answer 15

• Vaccination against an antigen you know is the tumor

Question 16

Neoantigen targeted therapies

Answer 16

vaccination against a non virus related protein

Question 17

Antigen therapy - tumor associated proteins

Answer 17

Therapy against proteins that are enriched in tumor cells

Question 18

Checkpoint blockade

Answer 18

PDL-1 on tumor cells can bind to PD1 on T-cells –> T-cell inhibited