Cancer immunology Flashcards by Roaa Alanbari

…………..is one of the tumor antigens and tumor markers that raised in ovarian cancer

CA125

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…………ensures that lymphocytes specific for different antigens keep on moving from circulation to the peripheral lymphoid organs.

Lymphocytes recirculation

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The stages of Immunoediting of cancer cells :

1-(Elimination) refers to effective immune surveillance for clones that express TSA.
2-(Equilibrium) refers to the selection for resistant clones (red).
3-(Escape ) refers to the rapid proliferation of resistant clones in the immunocompetent host.

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RAS protein which is normally [Active or inactive]

inactive

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BRCA1, BRCA 2 are Mutated [oncogene/Tumor suppressor gene] products

Tumor suppressor gene

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BCR/ABL Fusion proteins is Mutated [oncogene/Tumor suppressor gene] products

oncogene

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HER2/NEU is Mutated [oncogene/Tumor suppressor gene] products

oncogene

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RAS is Mutated [oncogene/Tumor suppressor gene] products

oncogene

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WT genes is Mutated [oncogene/Tumor suppressor gene] products

Tumor suppressor gene

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BRCA1 & BRCA2: genes for……….. cancer

breast

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HER2/NEU is growth factor receptor usually seen in………. cancer and known as………..

1-breast
2-ERBB2

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Example of Overexpression of normal proteins in the tumour antigen:

1-Tyrosinase, in melanoma
2-Cancer-testis antigens (CTA)

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…………………. And ………………identified CTA ( Cancer-testis antigens) as ideal targets for tumor-specific …………….and……………..

1- The tumor-restricted pattern of expression and strong in vivo immunogenicity

2- immunotherapeutic and vaccine therapy

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Examples of Cancer-testis antigens (CTA) is :

1-MAGE (Melanoma Antigen Gene) family of genes
2- BAGE

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Tumor Antigens include products of

1- mutated proto-oncogenes and tumor suppressor genes .
2-Mutated self proteins.
3- overexpressed or aberrantly expressed proteins.
4- viral oncogenic antigens.
5-onco-fetal antigens.
6- altered glycolipids and glycoproteins.
7- cell type–specific differentiation antigens.

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Expressed during fetal (embryonic life), but normally are not expressed (silent)
during adult life.

Oncofetal antigens

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What it is the cause of expression of the oncofetal antigens in the cell cancer ?

the adults there is a repression of these genes normally. In the
cancer cells, this repression is removed, what we call (de-repression)

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What is the types of oncofetal antigens ?

Alpha Feto-Protein (AFP)
Carcino-Embryonic Antigen

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What is the difference between Alpha Feto-Protein (AFP) and Carcino-Embryonic Antigen ? ( areas of the cancer )

Alpha Feto-Protein (AFP) in hepatocellular (Primary liver cell carcinoma)
carcinoma and some germ cell tumors (ovarian and testicular tumors)
Carcino-Embryonic Antigen in Colon, lung and other cancers

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What is the difference between Alpha Feto-Protein (AFP) and Carcino-Embryonic Antigen ? ( areas of the cancer )

Alpha Feto-Protein (AFP) in hepatocellular (Primary liver cell carcinoma)
carcinoma and some germ cell tumors (ovarian and testicular tumors)
Carcino-Embryonic Antigen in Colon, lung and other cancers

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What is the difference between Alpha Feto-Protein (AFP) and Carcino-Embryonic Antigen ? ( areas of the cancer )

Alpha Feto-Protein (AFP) in hepatocellular (Primary liver cell carcinoma)
carcinoma and some germ cell tumors (ovarian and testicular tumors)
Carcino-Embryonic Antigen in Colon, lung and other cancers

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We can detect B cell lymphoma by their expression of…………

CD20

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Example of Cell type specific differentiation proteins in tumor antigen is :

CD-20 in B cell lymphoma

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CD-20 in B cell lymphoma is example of :

Cell type specific differentiation proteins in tumor antigen

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Examples of Altered Cell Surface Glycolipids and Glycoproteins are :

Glycolipids : Gangliosides, Glycoproteins : blood group antigens + mucins (CA-125 and CA-19-9, expressed on ovarian carcinomas & MUC-1, on breast carcinomas)

The most important cells in killing tumor and tumor associating cells and in determining the effective immunity against tumor cell are………………

CD8+ t lymphocyte

Driver mutations /Passenger mutations in oncogenes and tumor suppressor genes that initiate transformation and confer growth self-sufficiency

Driver mutations

Driver mutations /Passenger mutations due to genetic instability that confer hallmarks of cancer and survival advantage.

Passenger

*We can find Cancer-testis antigens (CTA) in the ………. And ……. * if these genes get expressed in cells other than testis and placenta = …….………

1- testis 2- placenta. 3- tumor

………………….. is a tumor marker for hepatocellular carcinoma and some germ cell tumors (ovarian and testicular tumors) …………………..is a tumor marker for colon and lung cancer. *Hint: the answers are Oncofetal antigens

Alpha Feto-Protein (AFP) Carcino-Embryonic Antigen

The CD20 antigen is restricted to B cells. Its expression starts at the…….. of B cell ontogeny and continues until the………… stage. CD20 is not expressed on either precursor lymphoid cells or in the vast majority of plasma cells

1- pre-B stage 2- immunoblast

…………is a monoclonal (anti CD20) that we can use to treat CD20 in B cell lymphoma.

Rituximab

CA-125 is important for diagnosis and prognosis for……….. cancer

ovarian

MUC-1 expressed on ……………

on breast carcinomas

…………and………..expressed on ovarian carcinomas

1-CA-125 2- CA-19-9

Hepatitis B virus leads to ………….

Hepatocellular carcinoma

Human papillomavirus leads to …………..

Cervical cancer and other anogental neoplasm

Human Herpesvirus 8 (HHV8) leads to …….

Kaposi’s sarcoma

Epstein Barr virus ( EBV) leads to ……….

1-Nasopharyngeal carcinoma 2- Hodgkin’s lymphoma 3- Burkitt’s lymphoma 4- Lymphomas

Merkel cell polyomavirus (MCPyV) leads to ………..

Merkel cell carcinoma

Human T-cell lymphoma virus leads to ……….

Adult T-cell lymphoma/ leukaemia

…………… proteins in EBV-induced Lymphoma

EBNA

Antigens derived from inside the cell called ………………. antigens. processed and presented by………………. pathway ➡️ recognized by…………….

1-endogenous 2- MHC 1 3- CD8+ cells

Antigens derived from outside the cell are ……….. antigens. processed and presented by……………. pathway

1- exogenous 2- MHC 2

We have two types of responses - The……… against endogenous and intracellular proteins. - The ………response is against exogenous proteins. - The tumor antigens are produced inside the cells and against such cells so we need………….. response

1- CTL (CD+8) 2- T helper cell 3- CTL

………….recognize only protein antigens, while ………….recognize proteins, carbohydrates,nucleic acid, lipids, …etc.

1-T-lymphocyte 2- B-lymphocyte

Presentation of tumor neoantigens with MHC class I molecules is ………..……..

(antigen cross-presentation)

For the activation of T lymphocyte, the activation signals are classified into three classifications What is the signal 1?

Signal 1 is engagement of MHC I antigen complex with TCR (T-cell receptors).

For the activation of T lymphocyte, the activation signals are classified into three classifications What is the signal 2 ?

Signal 2 is engagement of the costimulatory molecules CD28 on T-cell and B7 on the dendritic cells.

For the activation of T lymphocyte, the activation signals are classified into three classifications What is the signal 3 ?

Signal 3 cytokine release: 1-- perforin: a protein which produces perforation in the membrane. 2- - Granzyme: cytolytic enzymes thatproduces protein lysis and apoptosis.

CD8+ T lymphocytes expresses ………………..which has the same ligand of CD 28 (i.e., B7). Thus, B7 could bind with both …………and……….. If B7 binds with CD 28, it sends stimulatory signals and T cell will be……….. On the other hand, if B7 binds with CTLA-4, it will send …………….signals and T cell will be inactivated

1- CTLA-4 2-CD28 and CTLA-4. 3-activated 4- inhibitory

The difference between extracellular and intracellular ( regions of CAR-T Cell)

1- extracellular part : which is antibody directed against tumor antigen 2–intracellular domain that deliver activating signals.

Ø Tumors that fail to express MHC class I antigens cannot be recognized by……… cells, but may trigger…… cells. Ø NK cells recognize MHC I negative cells through…… proteins that bind with stress induced antigens on transformed cells.

1- T cells 2- NK cells ( Natural Killer Cells) 3- NKG2D

Lytic activity of NK cell is enhanced with………...

IL2

………..cells are particularly useful against tumor cells which stopped expressing MHC-1.

Tumor cells decrease expression of MHC1 to escape CTLs, but then they get caught by…………

Natural Killer cells.

PD-1 (on CTL) and PD-L1 (on tumor cells) are important immune………. Inhibitors of……… function.

1-checkpoint 2- CTL (suppress CTL function )

Aberrantly expressed ( tumour antigens) are : 1- ……… 2- ……….

1- MAGE 2-BAGE

Human papilloma virus……….. and ………..proteins in the cervical carcinoma …………… proteins in the EBV induced lymphoma

1- E6 + E7 2- EBNA

…………… Cell-mediated immunity is the dominant antitumor mechanism in vivo

Cytotoxic T Lymphocytes

What are the function of Cytotoxic T Lymphocytes:

1-MHC-restricted CD8+ cells can kill autologous tumor cells 2-Protective role against virus-associated neoplasms (e.g., EBV induced Burkitt lymphoma, HPV-induced tumors).

steps of Immune reactions to cancers :

1- Presentation of tumor neoantigens with MHC class I molecules (antigen cross-presentation) 2- Recognition by antigen-specific CD8+ T cells 3- Activation, Proliferation and Differentiation into active CTLs 4- Homing to the site of the tumor 5- Recognition and killing of tumor cells. I

CD8+ T lymphocytes could be activated by………. and this activation could be enhanced by………….. CD4+ T lymphocyte will release…………….. which is an activator of CD8+ T lymphocyte and this is called antigen cross presentation.

1- dendritic cells 2- CD4+ T lymphocyte 3- interferon gamma (IFN-γ)

PD-1 on ………….and PD-L1 on ………is an important immune checkpoint. • PD-1, PD-L1 interaction leads to…………..

1-CTL 2-tumor cells 3- CTL unresponsiveness

………….: a protein which produces perforation in the membrane.

perforin

……………: cytolytic enzymes that produces protein lysis and apoptosis

- Granzyme

B7 can bind to both……. and………..

1-CD28 2-CTLA-4

When B7 binds to CD28, it transmits [stimulatory/ inhibitory] signals to the T cell, leading to T-cell [activation/ inactivation]. if B7 binds to CTLA-4, it sends [stimulatory/ inhibitory] signals, resulting in T-cell [activation/ inactivation]. . The binding of B7 to CTLA-4 acts as …………….

1- stimulatory 2- activation 3- inhibitory 4-inactivation 5- a regulatory mechanism to prevent excessive or prolonged T-cell activation.

So there are 2 immune checkpoints blockages that we are directing at to activate CTLs and prevent their blockage: 1- 2-

1. Anti-PD-1 Anti-PD-L1 monoclonal antibodies 2. And anti-CTLA-4 monoclonal antibodies

What is the function of CAR-T cells?

CAR-T helps T-cells attach to specific cancer cell antigen.

Patient………. are harvested and engineered to express chimeric antigen receptors (CAR).

CTLs

T cells, NK cells, and macrophages may collaborate in antitumor reactivity, because…………, secreted by T cells and NK cells, is a potent activator of macrophages

IFN-γ

Activated macrophages kill tumors by mechanisms similar to those used to kill microbes : 1 - ……………………. 2- or by secretion of………….

1- (production of reactive oxygen metabolites) 2- TNF

Tumor immune evasion mechanisms include :

1.Selective outgrowth of antigen-negative variants. 2- Loss or reduced expression of histocompatibility molecules MHC I genes. 3- Immunosuppression. 4. Antigen masking

The tumor cells can induce tumor suppression by different mechanisms (examples) :

ØProduce immunosuppressive cytokines like TGF-β. ØEngagement of the T cell inhibitory receptor, CTLA-4 ØActivation of regulatory T cells. ØMay express FasL that engages with Fas on immune cell and induce the apoptosis.

………….which is an inhibitory cytokine that inhibit the proliferation of lymphocytes. Therefore, they inhibit the immune response

TGF-β

Antigen masking: tumor cells can cover their surface with………. molecule which can prevent the binding of antigen specific immune cells.

1- glycocalyx

The cell surface tumor antigen may be hidden from the immune system by glycocalyx molecules such as……... This phenomenon is called………

1- sialic acid 2- antigen masking

…………….. Thick coat of external glycocalyx molecules, (sialic acid–containing mucopolysaccharides, than normal cells). *Access to immune cells is blocked

antigen masking