Chapter 319 - Cancer Immunotherapy Flashcards
What are the two primary immune cells responsible for direct tumor killing?
Cytotoxic effector CD8 T cells and activated Natural Killer (NK) cells
What is the role of regulatory T cells (Tregs) in cancer immunity?
Tregs downmodulate tumor immunity and serve as a check on excessive T cell activation to prevent autoimmunity
What strategies do tumors use to avoid immune elimination?
- Secreting immune suppressive molecules (e.g., IL-10, TGF-beta)
- Producing enzymes that deplete T cell metabolites
- Downregulating MHC molecule expression
- Losing tumor antigen expression
- Mutating cytokine signaling pathways
What are the key characteristics of effective innate immune activation in cancer treatment?
- Must be applied repetitively
- Sustained for relatively long periods (months)
- Activated to high levels, approaching immune toxicity
What are some key immune cells that can suppress tumor immunity?
Monocytes, neutrophils, and tumor macrophages (collectively known as myeloid cells)
What is the Oncept vaccine?
A canine vaccine targeting the melanoma antigen tyrosinase, approved for treating melanoma in dogs
What are the primary checkpoint molecules initially targeted in human cancer immunotherapy?
CTLA-4, PD-1, and PD-L1
What is a Chimeric Antigen Receptor (CAR) T cell?
A T cell that has been engineered in vitro to express a receptor specifically targeted to a tumor antigen, allowing more precise tumor cell destruction
What role do CD4 T cells play in cancer immunity?
They do not directly kill tumor cells, but are essential in initiating and sustaining tumor immunity and supporting the activity of CD8 T cells
How do NK cells differ from T cells in terms of activation?
NK cells can be activated directly by tumor cells without needing antigen-presenting cells, unlike T cells
What two drugs have shown promise in modulating the innate immune response in dogs?
Losartan (targets inflammatory monocytes) and Propranolol (targets immune suppressive monocytes and neutrophils)
What is the key process in initiating cancer immune responses?
The dendritic cell-T cell interaction, which regulates the initial activation and expansion of effector T cells and generation of memory T cells
What types of cancer are most likely to respond to immune checkpoint blockade?
Cancers with high numbers of infiltrating T cells, such as melanomas, uroepithelial cancers, and some high-grade sarcomas
