Systemic immunotherapy of solid cancers

Question 1

How are solid tumors like melanoma, renal or bladder cancers mostly treated?

Answer 1

With immune checkpoint inhibitors like CTLA-4/PD-1.

Question 2

What is the difference between CTLA-4 and PD-1 treatment?

Answer 2

In CTLA-4 (Cytotoxic T-lymphocyte antigen-4) treatment you activate T-cell in the lymphnode and in PD-1 (Programmed Death-1) treatment you activate T-cells in the TME. This is why you see a difference in side effects. The side effects for CTLA-4 are worse than for PD-1.

Question 3

What is needed to improve response rates to immune checkpoint inhibitors?

Answer 3

biomarkers for patient selection and response to treatment, mechanisms for resistance, timing, and combinations of therapy.

Question 4

What is pseudo-progression?

Answer 4

The kinetics of immunotherapy is much different, you induce an inflammation so the tumor will get worse before it gets better (pseudo-progression).

Question 5

How does inhibition of angiogenesis improve immune cell infiltration?

Answer 5

Targeting angiogenesis normalizes the vasculature so T-cell can enter the tumor.

Question 6

What are examples of pathways we can target to modify the anti-tumor immune response?

Answer 6

BRAFi for example decreases the immunosuppressive cytokines and VEGF and increases PD-L1. This is also shown for MEKi and BRAFi/MEKi combinations.
When you combine these inhibitors with immune checkpoint inhibitors you have a synergistic effect (the combined effect is bigger than individual effect).