Tumor Immunology Flashcards
what role does the immune system play in preventing cancer?
catches onto tumor cells that express viral proteins / aberrant self proteins & → eliminates them
what are the categories of tumor cell proteins?
- oncofetal antigens
- overexpressed normal proteins
- immunoglobin antigens
- mutant cellular proteins
- oncogenic virus proteins
oncofetal antigens
- are which antigens?
- are expressed by what tissues?
- response to tx?
AFP, CEA
- normally ONLY expressed during embryogenesis
- include
- carcinoembryonic antigen (CEA): esp elevated in colon cancer
- alpha-fetoprotein (AFP): esp elevated in liver cancer
- should decline & stay low if tx is successful
what does it mean if CEA/AFP levels rise after cancer tx?
the cancer metastasized, and wasn’t all removed by surgery
which tumor antigens are over-expressed normal proteins?
what tissues are they typically seen in?
- HER-2:
- breast cancer
- ovarian cancer
- CA-125
- ovarian cancer
- endometrial / peritoneal inflammation
- PSA:
- prostate cancer
- benign prostatitis
immunoglobin antigens
- include what antigens?
- are expressed by what tissues?
- both made during multiple myeloma, which is proliferation of plasma B-cells in the bone → “punch lesions in skeleton”
- M-protein = MONOCLONAL IG
- Bence-jones protein = LIGHT CHAINS
what is the most common cause of primary neoplasm in the skeletal system?
multiple myeloma
where are bence-jones proteins most likely to be found?
= light chains d/t multiple myeloma
in the urine
multiple myeloma -“punch lesions” in skeleton
multiple myeloma - thick bands = many of one type of Ig being made from proliferating plasma B-cells
mutant cellular gene products
- includes which antigens?
- expressed by what mechanisms / tissues?
= d/t activation of proto-oncogenes
-
heavy chain locus:
- in Burkitt’s lymphoma
- d/t c-myc translocation following an EBV infection
-
mature granulocytes
- in chronic myelogenous leukemia
- d/t reciprocal translocation between BCR & ABL
burkitt’s lymphoma
- mechanism / cause
- produces what type of tumor antigen?
- presentation
- antigen type: mutant cellular gene products (activation of proto-oncogenes)
- EBV infection results in c-myc translocation → heavy chain locus (antigen)
- presentation - see picture
chronic myelogenous leukemia (CML)
- mechanism / cause
- produces what type of tumor antigen?
- presentation
- antigen type: mutant cellular gene products (proto-oncogene activation)
- reciprocal translocation of BCR & ABL- genes → mature granulocyte proliferation (antigen)
- presentation - n/a
what are the presentations of the following oncogenic viral infections?
- EBV
- HTLV-1
- HTVL-2
- HPV
- HBV, HCV (hepatitis)
- HHV-8
vaccines are available for which oncogenic viruses?
- HPV - cervical cancer
- HBV (hepatitis B) - liver cancer
what are the means by which we can detect tumor antigens?
-
RAI (radioactive iodine marker):
- can be used to detect all tumor antigens that shed into the blood/urine:
- embryonic antigens: CEA, AFP
- normal antigens that are over expressed: CA-25, PSA
- myeloma antigens: M-protein, Bence Jones protein
- can be used to detect all tumor antigens that shed into the blood/urine:
other detection methods:
- myeloma antigens: with
- electrophoresis
- radiography - punch biopsy
- mutant cellular gene products: with
- cytogenic analysis - detects translocations
what can the “FISH” technique tell us?
the # of copies of specific oncogenes
outline the immune response to tumors
- involves unique players:
-
macrophages - M1, M2
-
M1 (anti-tumor)
- = PRO-INFLAMMATORY + ANTI-TUMOROGENIC
- TNF-a, IL6, 12, 23 → inflammation → cell lysis
- = PRO-INFLAMMATORY + ANTI-TUMOROGENIC
-
M2 /TAMs (protumor)
- ANTI-INFLAMMATORY + PRO-TUMOROGENIC
- TGF-B, IL-20 → immunosuppressive
- metalloproteinases → facilitate tumor cell migration
- ANTI-INFLAMMATORY + PRO-TUMOROGENIC
-
M1 (anti-tumor)
-
macrophages - M1, M2
M2 cells
- are what type of cell?
- have what role?
- are produced in what context?
- are specialized macrophages involved in tumor immunity
- are anti-inflammatory & pro-tumorigenic. produce
-
IL-10, TGF-B →
- immunosuppression
- fibrosis - encapsulates & protects tumor
- angiogenesis - vessel growth within tumor
- metalloproteinases → remodel vasculature to facilitate tumor cell migration
-
IL-10, TGF-B →
- are favored in a tumor microenvironment
M1 cells
- are what type of cell?
- have what role?
- are produced in what context?
- are specialized macrophage cells involved in tumor immunity
- are pro-inflammatory & anti-tumorigenic - the “good guys”
- TNF-a + IL6, 12, 23 → inflammation + cytotoxicity
- proliferate in response to
- INF-y
- LPS
- TLRs
what is the goal of cancer therapy?
- overall: to skew the predominant macrophages from M2 → M1
- for bladder cancer: instillation of BCG provides TLRs → M1
what is the role of NK cells in tumor immunity?
= innate immunity
-
NK cells initiate ADCC of tumor cells
- can detect that have down regulated their MHC-I expression to hide from Tc cells with key receptors:
- CD16: binds Fc portion of IgG (whose arms are bound to tumor cell antigen)
-
KIR receptors: who CANNOT bind cells with no MHC-I
- lack of binding sends positive signal of NK cell to → INITIATE ADCC
- can detect that have down regulated their MHC-I expression to hide from Tc cells with key receptors:
what is the role of B-cells the tumor immunity?
= adaptive immunity
produce antibodies (IgG) that participate in ADCC
what are the means by which tumors evade our immune system?
- up regulation of PDL-1 expression → Tc inactivation
- secrete TGF-B & IL-10 → T-cell suppression
-
evasion of T-cells
- antigen loss variants (tumors that don’t express antigen)
- Class I MHC down-regulation → evades Tc
- Lack of B7 → evades Th
- BCL-2, STAT-3 → prevents apoptosis
what is PD-L1?
how does it work?
- a ligand expressed by tumor cells that interact with T-cells that express PD-1 receptor, and → inactivates the Tc
what is the role of class I MHC down-regulation immune system evasion by tumor cells?
- helps them escape Tc
- however, allows them to be seen by NK Cells KIR
what tumor cell products can prevent their apoptosis?
- BCL-2
- STAT-3
what are the methods of immunotherapy to treat cancer?
- Mabs - retiuximab, trastuzumab, bevacizumab
- Checkpoint inhibitors - nivoloumab
-
Adoptive cell transfer
- CAR-T
- TILs
- LAK cells
- cytokine therapy
list the Mabs (monoclonal antibodies) that can be used as cancer immunotherapy?
what type of cancer does each treat?
- rituximab - targets B-cell cancers: targets CD20
- trastuzumab - targets breast/ovarian cancer → targets HER-2
- bevacizumab → VEGF (many cancers)
what is nivolumab & its role in immunotherapy?
- is an immune checkpoint inhibitor
- binds & blocks PD-L receptors on activated Tc cells so that they cannot be bound by tumor cells that express PD-L1 → keeps them activated
rituximab?
tx of cancerous B-cells
targets CD20
trastuzumab
tx of breast / ovarian cancer
targets HER-2
bevacizumab
tx of many cancers
targets VEGF
list the adoptive cell transfer (ACTs) that can be used as immunotherapy?
what do they all have in common?
- CAR-T
- TILs
- LAK cells
all are lymphocytes that are exposed to IL-2 so that they proliferate
CART T-cells
- are engineered how?
- treat what type of cancer?
- T-cells taken out of individual & genetically engineered to express an surface antigen-receptor with two domains
- ectodomain: contains surface receptor that binds a specific tumor antigen
- endodomain: intra-cytoplasm region that conducts signal for Tc cell to be → cytotoxic
- exposed to IL-2 to → proliferate
good to treat LEUKEMIAS
