what is banign?
unable to invade healthy surrounding tissue, incapable of indefinite growth
what is malignant?
becomes progressively more invasive, may metastasize
what is metastasis?
the spread of cancer cells beyond the site of origin
what are the hallmarks of cancer?
stimulating their own growth
ignoring growth-inhibiting signals
avoiding death by apoptosis
developing a blood supply: angiogenesis
seeding from site of origin to invade other tissues: metastasis
constant replication to expand the tumor-cell population
evasion and outrunning the immune response
what are the cancers of the immune system/blood?
leukemia
lymphoma
myeloma
leukemia
a group of cancers that begin in the bone marrow and lead to overproduction of white blood cells
lymphoma
neoplasms of the lymphatic tissues; usually lymphocytes
myeloma
cancer of the plasma cells; they can accumulate in the bone marrow and then secrete abnormal antibodies
what are proto-oncogenes
genes that regulate control of cell growth and division; when mutated can contribute to malignant growth of cells
what are tumor-suppressor genes?
genes that encode proteins which normally function to prevent cells from becoming cancerous; may also include genes that control apoptosis
what are the four stages of malignant transformation?
initiation
promotion
progression
metastasis
what are the four types of environmental factors that can cause cancer?
chemicals
UV light
radiation
oncogenic viruses
what are tumor antigens?
cells are self cells that may express either unique or inappropriately expressed Ag that can be detected by the immune system
what are the four groups of tumor antigens that are recognized by the immune system?
Ag encoded by genes exclusively expressed by tumors
Ag encoded by variant forms of normal genes altered by mutation
Ag normally expressed only at certain stages of development
Ag overexposed in particular tumors
what are tumor-specific antigens?
antigens specific to tumor cells, not found in non-cancer cells
what are tumor-associated antigens?
normal cellular proteins; not unique to cells
what are the three phases of immunoediting?
elimination
equilibrium
escape
elimination
also known as immunosurvelliance; innate and adaptive immunity
equilibrium
at this stage, the tumor is considered to be dormant; it is decreased in terms of its immunogenicity. the immune system has a hard time recognizing the altered tumor
escape
tumor cells with low immunogenicity can evade immune system detection
how do tumor cells evade immune defenses?
subversion of MHC class I
sabotage of apoptotic signals
poor co-stimulation
T cell exhaustion of tolerance
what are the five types of immunity?
monoclonal antibodies
adaptively transferred DCs
adaptively transferred T cells
CAR T cells
checkpoint/blockade therapy
monoclonal antibodies
treatment of terminal B-cell lymphoma with anti-idiotype mAb
mAb against CD20 B-cell marker for non-hodgkin's lymphoma
immunotoxins, toxic molecules coupled to mAb
mAb against HER2 receptor in breast cancer
adaptively transferred DCs
isolate autologous DCs
co-culture DCs with antigen
re-infuse antigen loaded DCs into patient
patient has increased CD4+ and CD8+ T cell response against tumor antigens, stimulating a stronger CTL response
adaptively transferred T cells
cells obtained from tumors, tumor-draining nodes, or peripheral blood
once obtained, the cells are expanded ex vivo using IL-2 cytokine to overcome anergic states
patients are depleted of lymphocytes to create a niche for the new cells
the expanded cells are reinfused
what are CAR T cells?
chimeric antigen receptor
what are the types of CAR T cells?
truck
universal CAR
self-driving CAR
armored CAR
self-destruct CAR
conditional CAR
checkpoint/blockade therapy?
manipulation of costimulatory signals can improve cancer immunity