Tumor Immunology Flashcards

1
Q

How does anti-tumor immune response differ against syngeneic vs allogeneic tumors?

A

Syngeneic - no response (seldom rejected)

Allogeneic - often rejected, due to different MHC haplotype

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2
Q

What are the three phases of immunosurveillance?

A
  1. Elimination phase - immune system finds and destroys potential cancers
  2. Equilibrium - elimination is not completely successful and tumors immunoedit
  3. Escape phase - tumors start growing unimpeded after sufficiency mutations
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3
Q

What are the “distress signals” associated with tumor cells? What recognizes them?

A

DAMPs - damage associated molecular patterns

  • include HSP, HIF (hypoxia-inducible factor), KAR ligands,
  • Recognized by macrophages, dendritic cells (TLRS) and NK cells
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4
Q

What type of antibodies are found in the patient’s serum during the escape phase and what does this indicate?

A

IgM more prevalent -> lack of T cell help

Tumor-infiltrating lymphocytes will become unresponsive

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5
Q

Give two tumor types common in immunosuppressed patients

A
  1. Kaposi’s sarcoma - HHV8
  2. Burkitt’s lymphoma- EBV (HHV4)

Herpes and epstein barr

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6
Q

What are the two types of receptors on NK cells?

A
  1. KIR (i.e. NKG2A)- killer inhibitory receptors - bind MHC Class 1 to prevent NK cytotoxicity
  2. KAR (i.e. NKG2D) - killer activating receptors - bind MIC-A or MIC-B on tumor and activate lysis
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7
Q

What are MIC-A and MIC-B?

A

Glycoproteins related to MHC Class 1 which can activate NK cells via NKG2D receptor when they are expressed

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8
Q

Do NK’s have TLRs?

A

Yes, they can also be induced by TLR3 and TLR1 - activated by DAMPs

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9
Q

Why does downregulation of MHC Class 1 target cells for NK destruction?

A

Loss of KIR signal, swinging favor of KAR-induced cell death

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10
Q

When do cancers express KAR ligands?

A

During neoplastic stress, making them susceptible to lysis by NK cells

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11
Q

What two cytokines are antitumor and why?

A

IFN-y -increase inflammation and immune response

IL-12 - third signal needed for T cell activation

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12
Q

What four cytokines are pro-tumor?

A
  1. TGF-beta - immune suppression
  2. IL-10 -immune suppression
  3. IL-6 - inflammatory, but important tumor growth factor
  4. VEGF - for angiogenesis
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13
Q

What two cytokines are contextual in their effect?

A
  1. IL-2 - could also stimulate Treg population

2. TNF-alpha - could also activate tumor cells

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14
Q

What cell type is needed for the elimination but no equilibrium phase?

A

NK cells -> do not play a significant role in inhibiting tumor growth during equilibrium phase

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15
Q

What are some changes in tumor cells that can mediate immune escape?

A
  1. Antigen loss variant - loss of antigen not needed for growth / proliferation
  2. Reduction of MHC 1 expression
  3. Modulation of apoptosis genes - resistance to Fas and caspase-mediated apoptosis
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16
Q

What are the two macrophage phenotypes, and which one is pro tumor?

A
M1 = cytotoxic macrophage
M2 = suppressive, woundhealing macrophage which is pro-tumor
17
Q

How can tumors modify the immune response in their favor?

A

Polarization of immunity towards pro-tumor phenotype:

Induce Treg cells, M2 cells
Induce anergy via lack of co-stimulation
Secrete suppressive cytokines TGFbeta and IL-10

18
Q

What is an MDSC? What surface marker do they express?

A

Myeloid-derived suppressor cell which can be induced by tumors to downregulate T cell response using TGFb and PDL1

Express CD11b, and CD15+ is a granulocyte

19
Q

How might a tumor cell physically evade an immune response?

A

Growth in a nodule so areas are not accessible to T cells

20
Q

What other MHC Class 1 types can tumors express for escape?

A
  1. HLA-E - binds KIR on NK cells

2. HLA-G - silences NK cells, suppresses T cells and monocytes. Same marker express by fetal cells to avoid maternal MHC

21
Q

Why is downregulation of TAP good for tumor cells?

A

Reduced MHC 1 expression or MHC loaded with low affinity peptides
-> avoid CD8+ T cell killing and NK cell killing

22
Q

Why can mast cells be important for tumor growth?

A

Activated during inflammation, they release proteases which initiate angiogenesis

23
Q

What cytokines do tumor associated macrophages release to promote tumor growth?

A

Suppression: IL-10, TGF-beta, PDL1, arginase 1
MMPs for metastasis
VEGF for angiogenesis

24
Q

How do MDSCs activate Treg cells?

A

CD40-CD40L interaction to induce tolerance to tumor cell expressed antigen

25
Q

How do monocytic MDSCs differ from granulocytic?

A

Monocytic - use NO and cytokines

Granulocytes - use ROS (think of granules wanting to use reactive oxygen species)

26
Q

What is IL-10 normally used for, and what is its use in cancer?

A

IL-10 normally prolongs B cell life and antibody production

In cancer, it regulates MHC downregulation, tumor growth, metastasis, and EMT

27
Q

How can we stop tumor PDL1 expression?

A

Give antibodies to PDL1, to prevent use of PDL1 for apoptosis of immune cells

28
Q

What is the function of CD47?

A

Blocks phagocytosis by dendritic cell

29
Q

Why is Tim-3 a good antigen target? What is it functionally analogous to?

A

Expressed primarily in intratumoral cells

Analogous to PD1 / CTLA4

30
Q

Why are nonspecific approaches to cancer immune therapy not very good?

A

Use cytokines such as IL-2 which can also stimulate T-reg cells

31
Q

How does the dendritic cell based cancer vaccine work?

A

Activates both the cellular and humoral immune responses

Must sensitize and culture DCs in the presence of the resected tumor, and vaccinate the patient with these, while also expanded the T cell population ex vivo (combined therapy)

32
Q

What type of treatment is monoclonal antibodies for cancer considered?

A

An adoptive humoral treatment

33
Q

What is an adoptive cellular cancer treatment?

A

Infusion of ex vivo expanded tumor-reactive T cells

34
Q

What is a LAK cell?

A

Lymphokine active killer cell

35
Q

What is a TRA?

A

Tumor rejection antigen - an antigen specific for tumors of a specific type which can be used as a vaccine target

36
Q

What is antibody-dependent cell-mediated cytotoxicity (ADCC)?

A

Monoclonal antibodies can recruit NK cells to cause tumor cell lysis

37
Q

What is ADEPT?

A

Antibody-directed enzyme / prodrug therapy

-bring prodrug to tumor then activate with exnzyme

38
Q

What is immunodiagnostics?

A

Field of study by which monoclonal antibodies and tests can be used to determine tumor progression via various markers

39
Q

What is Gardasil prophylactic for?

A

HPV 16 and 18 causing cervical cancer

HPV 6 and 11 - causing genital warts