Tumor Immunology

Question 1

what is the best evidence that cancer immunosurveillance/ immune editing occurs?

Answer 1

tendency for immunosuppressed individuals to get cancer

Question 2

describe the 3 stages of immune editing

Answer 2

1. elimination- NK and T cells infiltrate and either eliminate or fail to eliminate the tumor
2. equilibrium- if they fail to eliminate the tumor, it enters a state of equilibrium where it is both constantly growing and other constant attack from the immune system.
3. escape- if the tumor mutates, making it less vulnerable to CD8 or NK cell attack, it can escape and grow clinically relevant

Question 3

what are the most important effectors against tumors?

Answer 3

CTLs and NK cells- most important

additionally

• CD4 helper cells play a supporting role
• B-cells can create Abs but their efficacy is unknown

Question 4

tumor specific antigens vs tumor associated antigens

Answer 4

TSA- only found on tumors

TAA- found on tumors and normal cells

Question 5

virally-induced cancers

Answer 5

cancers caused by virus are often immune suppressed because viral antigens are recognized as foreign. up to 60% of cancers may be caused by viruses and they are especially dangerous in immunosuppressed individuals

examples: EBV, HPV, Hep B and C

Question 6

mutated antigens

Answer 6

cancers are the result of mutations, and sometimes mutations in proteins cause them to be recognizable via the immune system. this can be either oncoproteins, mutated tumor suppressor genes, or proteins that didnt cause the cancer but are also mutated

Question 7

oncofetal antigens

Answer 7

inappropriately expressed fetal antigens can be found on tumors. these can be recognized by the immune system and can also be used for monitoring purposes.

Question 8

use of normal self-antigens as tools in cancer treatment

Answer 8

normal cellular antigens are expressed at different stages of cellular development. if a tumor forms, it will express some of these antigen markers. mAbs can be used to determine what stage of development of development malignancy occured

also, the idiotypes can be used as potential therapeutic targets of malignant B and T cells

Question 9

describe some mechanisms cancers use to avoid immune detection

Answer 9

tolerance- if a majority of tumor antigens are TAA, or if antigens is presented under conditions such that T cells are unresponsive (w/o costimulation)

selection for tumor negative variants- if antigens associated w/ tumor cells activate the immune system effectively, they will be eliminated. however, not all tumor cells express the same antigens and therefore these “tumor negative variants” will be left behind

tumor suppresses the immune system- release of TFG or IL-10

tumor has low immunogenicity- tumors that don’t have MHC-1 (also become more susceptible to NK response)

tumors induce T-regs and other suppressor cells- tumors recruit regulatory and suppressor cells and it allows them to survive

Question 10

describe the two potential dimensions of an immunocancer therapy

Answer 10

1. antigen specific vs non Ag specific

3. active vs passive

Question 11

describe non specific, active therapies

Answer 11

utilize nonspecific immunostimulants (BCG, C. Parvum, cytokines such as IFN-a and IL2) to activate the immune system and induce tumor killing. tumor death occurs d/t mediators released from activated effectors - macrophages.

Question 12

describe specific, passive therapies

Answer 12

Abs to tumor antigens are given to the pt

ex.

1. against the idiotype region of T or B cells
2. against a mutated epidermal growth factor receptor which acted as an antigen
3. Ritaximub
4. Herceptin (breast cancer)

cause cell death via complement activation, ADCC, inducing apoptosis, or ADCC

Question 13

describe non-specific, active therapies

Answer 13

mAbs to enhance immunostimulatory or block inhibitory pathways

eg. CTLA 4 blocking Abs that prolong T-cell activation

Question 14

describe specific, active therapies

Answer 14

vaccines

prophylactic- HPV

most vaccines are designed to enhance/induce effective tumor immunity in pts w/ cancer already.

examples:

whole tumor cells- inert tumor cells transfected to produce cytokines

protein vaccines- purified tumor antigen w/ adjuvant

peptide vaccines- MHC-1 or 2 peptide epitopes mixed w/ adjuvant

DNA vaccines- DNA encoding the tumor antigen is inoculated so that it can transfect APCs and they can cross present

Dendritic cells- Dcs loaded w/ peptides/ proteins/ whole tumor cells and injected into pts

Question 15

Adoptive T cell therapy

Answer 15

take T cells out of a tumor, expand them ex vivo, and reinfuse them back into pts. most of these t cells are already antigen specific, but t cells can also be engineered to express TCRs for specific antigens