tumor immunity

Question 1

characteristics of cancer cells

Answer 1

• stimulate their own growth
• ignore growth-inhibiting signals
• evade apoptosis
• develop a blood supply: angiogenesis
• metastasis
• replicate continuously
• evade immune response

Question 2

define tumor

Answer 2

(neoplasm)- cells growing abnormally

Question 3

define metastasis

Answer 3

spreading of cancer cells to distant sites, focus of new growth

Question 4

define malignant transformation

Answer 4

the process through which a cell becomes able to form cancer
- this involves accumulation of multiple mutations in genes that regulate cell division and cell survival

Question 5

difference between benign & malignant

Answer 5

benign- adenoma
- contained by fibrous connective tissue
- localized and limited in size

malignant- adenocarcinoma
- not limited by capsule, invasive, can break through basal laminae & invade adjacent tissues

Question 6

common sites for tumor development

Answer 6

• sites of lots of cellular turniver
• bone marrow, lymph glands, lungs, reproductive organs

Question 7

causes of cancer

Answer 7

1- environmental- often referred to as mutagens, carcinogens, oncogenic viruses
2- genetic- mutations in certain genes
. BRCA1/BRCA2- mutant forms of these tumor suppressor genes increase risk of breast and ovarian cancer by five fold (60% compared to normal 12%)

Question 8

genes whose product positively regulate cell division & function normally in normal cells

Answer 8

proto-oncogenes

Question 9

mutated versions of proto-oncogenes that contribute to malignant transformation

Answer 9

oncogenes

Question 10

encode proteins that prevent unwanted proliferation of mutant cells

Answer 10

tumor suppressor genes

Question 11

tumor suppressor gene- over 50% of of human tumors have a mutation in this gene

Answer 11

p53

Question 12

many human tumors are caused by viruses

Answer 12

1- DNA viruses:
. Papillomavirus- warts (benign), carcinoma uterus
. Hepatitis B virus- liver cancer
. Epstein-barr virus- Burkitt’s lymphoma
2- RNA viruses:
. HTLV-1- adult T-cell leukemia/lymphoma

Question 13

name 3 cancers of the immune system

Answer 13

1- leukemia- cancer of immune system cells
2- lymphoma- involving solid lymphoid tumors
3- myeloma- involving bone marrow

Question 14

how can the immune system recognize tumors as dangerous and target them for removal?

Answer 14

• tumor antigens
• cells that are malignantly transformed have genotypic differences that distinguish them from healthy cells
• antigens present on tumors cells, but not normal cells are called tumor-specific antigens
• antigens present on tumors but also normal cells ( at lower expression levels) are called tumor associated antigens

Question 15

describe tumor specific antigens

Answer 15

• present on tumor cells but not on normal cells (certain p53, ras, and B-catenin variants)
• products of oncogenic viruses (EBV and HPV)

Question 16

describe tumor associated antigens

Answer 16

• not necessarily unique to tumors
• overexpressed by tumors: Her2-Neu
• tumor-specific post-translational modificications, Muc-1 abnormal glycosylation and localization

Question 17

describe cancer/testis antigens

Answer 17

tumor associated antigens
- expression restricted to gametogenic tissues (immunologically privileged) and cancer
- genes frequently map to chromosome X (50%)
- immunogenic in cancer patients
- expression may be related to tumor progression and with tumors of high metastatic potential

Question 18

describe tumors and their immunogenic-ness

Answer 18

tumors may not be very immunogenic
- chemical or radiation-induced tumors as well as virally-induced tumors are generally immunogenic b/c of the generation of altered self
- however, many spontaneous tumors may not be very immunogenic
- an immune response against a self-antigen generally requires breaking self-tolerance

Question 19

describe immune evasion by tumors (best & worst case scenarios)

Answer 19

best-case scenario: tumor cell- has tumor specific antigens that can be recognized by MHC—> activation of T cell response

bad: tumor cell may not express tumor specific antigens, or MHC class I or they may express inhibitory ligands and immunosuppressive cytokines—> inhibition of T cell activation

Question 20

mechanisms of tumor-mediated immune suppression

Answer 20

secreted factors: IL-10, TGF-B, PGE-2 (all decrease the potency of anti-tumor effector cells)

• tumors can provide negative costimulation:
  CTLA-4/B-7 inteactions
  PD-1/PDL1 interactions
  downregulation of MHC

Question 21

TGF-B positively regulates ___

Answer 21

Treg cells —> immunosuppressant

Question 22

more mechanisms of tumor-mediated immune suppression

Answer 22

• T regulatory cells
• CD4+ and CD25low and/or Foxp3-Tregs
• suppressive activity mediated through secreted factors IL-10 and TGF-B
• in vivo depletion of Tregs through anti-CD25 treatment slowed the growth of transplantable tumors in syngeneic mice

Question 23

mechanisms of tumor defense

Answer 23

• innate immunity- Nk cells, macrophages, DC’s
• adaptive immunity- CD4+ and CD8+ T cells, more limited role for B cells

Question 24

NK cells and cancer

Answer 24

• mice lacking NK cells have faster growing tumors
• tumor cells that lack MHC molecules are sensitive to NK-mediated killing
• tumors can express ligands that activate NK-mediated killing
• NK cells express IFN-y and TNF-a which can inhibit tumor growth

Question 25

opportunities for immunotherapy

Answer 25

often, primary tumors are not eliminated by immune therapy alone
- after surgery and radiation, opportunities to fight metastases or silent tumors with immune therapy
- need to wait for restoration of immune system following certain chemo therapies

Question 26

cell-based immunotherapy for tumors, cell transfer

Answer 26

tumor-bearing patient- isolate lymphocytes from blood or tumor infiltrate
- expand in culture with IL-2 may be transfected with CAR gene
- transfer back into patient –> tumor regression

Question 27

monoclonal antibody therapy

Answer 27

monoclonal antibody directed against certain antigens expressed by tumor cells
- ex: CD20 antibody can be linked to a toxin, antibody homes to tumor and delivers toxin, leads to its destruction