281 - Tumor Immunology

Question 1

What is pseudoprogression after immunotherapy?

Answer 1

Tumor appears to grow at first

(probably due to lots of immune cells going there)

Be patient! Likely to regress later

Question 2

Briefly describe the oncolytic virus approach to treating melanoma

Answer 2

HSV-1 is re-engineered to fight melanoma -> TVEC

• TVEC is injected into tumor
• Causes tumor lysis, expression of GM-CSF in the microenvironment
• Attracts lots of immune cells
• -> anti-tumor response

Question 3

What is the difference between type 1 and type 2 macrophages?

Answer 3

Type 1 (M1) = turn on adaptive immunity

Type 2 (M2) = limits adaptive immunity

• M1’s are eager and excitable*
• M2’s are burnt out ard ready to limit activities*

Question 4

What is the most significant side effect of immune therapies?

Answer 4

Autoimmunity

• Goal is to maximize immune response to tumor, but also need to prevent autoimmunity*
• Rash/desquamation, colitis, hypophysitis, encephalitis*

Question 5

List 2 things that can prevent T-cell activation

1 during the priming phase, 1 in the tumor microenvironment

Answer 5

• Priming: T-cell can express CTLA-4
  
  • Binds APC’s B7 with higher affinity than T cell’s CD28
  • CD28 needed for secondary activation; if CTLA-4 binds B7, B7-CD28 interaction cannot occur and T-cell does not activate
• Tumor environment: Tumor cell can expres PD-L1
  
  • Binds to T-cell PD-1 receptor
  • Prevents T-cell activation
  • Anti-PDL1 or Anti-PD1 therapies prevent this interaction, allow the T-cell to become active

Using a combo of Anti-PDL1 and anti-CTLA4 = helpful!!

Question 6

Which cells activate T cells via the T cell recpetor?

Answer 6

Dendritic cells

Causes T cells to differentiatie into CD4+ helper or CD8+ cytotoxic

Dendritic cells = key link between innate and adaptive immunity

Question 8

What are the primary and secondary signals that work together to activate T-cells?

Answer 8

• Primary
  
  • APC presents antigen on MHC to T-cell receptor
• Secondary
  
  • APC expresses B7, which binds to CD28 on the T-cell

If T-cell expresses CTLA-4, it has a higher affinity for B7 than CD28; will prevent activation

Question 9

How does the immune system normally work to fight cancer?

Answer 9

• Innate immune cells cause cancer lysis
  
  • Antigen-indeepndent process
  • Creates tumor neoantigens
• Dendritic cells uptake neoantigens
  
  • Express to T-cells; antigen dependent
  • Activates the adaptive immune system
• T-cells become activated
• ​CD8+ cytotoxic T cells go to the tumor
  
  • Antigen-dependent cell death
  • Goal is to shrink tumor

Things in blue = drugs that can augment this system

Question 10

How do tumors evade the immune system?

Answer 10

• Equilibirium
  
  • Tumor cells are there, but they are dormant - hiding from the immune system
• Escape
  
  • Tumor figures out how to take over without being caught by the immune system

Question 11

Which cells are involved in the innate and adaptive immune systems?

Answer 11

• Innate
  
  • Macrophages
  • Dendritic cells
  • NK cells
  • Neutrophils
• Adaptive
  
  • T cells
  • B cells