Cancer Immune Response and Tumor Evasion Mechanisms

Question 1

What is immunosurveillance?

Answer 1

A protective immune system function to recognize and destroy cancerous tumor cells. It includes actions by CTLs and NK cells

Question 2

Can an inflammatory response act a cancer?

Answer 2

Yes because it can promote cytokines that enhance growth. OR it can enhance responsiveness and destruction of a tumor

Question 3

Define tumor specific antigens

Answer 3

Antigens that are unique to tumor cells. They can exist in tumors with cancer-associated viruses (oncogenic viruses) or from mutated self antigens

Question 4

Define tumor associated antigens

Answer 4

Antigens expressed on other healthy tissues and in cancer cells. Requires loss of tolerance to be recognized by the immune system.
These can occur with normal antigens on proteins in immunologically privileged sites OR
if they are reactivated from embryonic genes OR expressed at higher levels in cancer cells compared to norm tissue

Question 5

Define cancer tolerance

Answer 5

Immune system is tolerant to predominant antigen (there are no tumor specific antigens) OR
T cell repertoire is tolerant to tumor antigens

Question 6

List tumor immune system evasion mechanisms

Answer 6

1. tolerance
2. down modulation of MHC class I expression (CTL espcape)
3. NK cell inhibition
4. general inhibition of immune response - cytokines, Tregs
5. tumor load is too great

Question 7

Explain MHC class I down regulation

Answer 7

Down regulation of MHC class I allows evasion by CTLs detection of specific tumor antigens, which leads to a survival advantage

Question 8

Explain NK cell inhibition

Answer 8

1. The tumor may have the ability to block recognition of a stress-induced surface protein called MIC (minimum inhibitory concentration) which is often expressed on cancer cells
2. Tumor cells may also gain ability to secrete MIC which can bind to NK receptors, blocking tumor recognition and destruction

Question 9

Explain general immune system suppression by tumors

Answer 9

Tumor develops ability to secrete inhibitory cytokines like TGF-beta and IL-10, which inhibit proliferation of B and T cells.
Many tumors associated with Treg cells that can block activation of tumor infiltrating T cells

Question 10

Explain tumor load as an evasion mechanism

Answer 10

The tumor load is already substantial before malignancy detected. It may go undetected if there are no detectable tumor antigens or cellular damage or immune response