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The Immune System & Cancer Flashcards

1
Q

The Immune System & Cancer

Cancer cells

what triggers a mutation?

A

Mutations triggered by chemicals,
radiation, viruses, or inherited defects
in regulatory genes

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2
Q

The Immune System & Cancer

Cancer cells

After a mutation is triggered what happens?

A

Cells proliferating in an uncontrolled
fashion will give rise to a growing
clone of cells that eventually develops
into a tumor or neoplasm

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3
Q

The Immune System & Cancer

Cancer cells

what mechanisms are involved in tumor supression?

A

Several mechanisms are involved in
tumor suppression: DNA repair,
cellular senescence, etc

Apoptosis

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4
Q

The Immune System & Cancer

Cancer cells

Tumor Antigens
Name 3

A
  • Neoantigens
  • Oncogenic Viruses Antigens
  • Overexpressed Cellular Proteins

see slides for diagrams

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5
Q

The Immune System & Cancer

Cancer cells

Tumor Antigens

what is a neoantigen?

A
  • Neoantigens
    – Encoded by mutated genes
    – Not found on normal cells
    – A single tumor can express several neoantigens
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6
Q

The Immune System & Cancer

Cancer cells

Tumor Antigens

what is a Oncogenic Viruses Antigens

A

Oncogenic Viruses Antigens
– May elicit responses against the tumors
– Epstein-Barr virus, Papillomavirus

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7
Q

The Immune System & Cancer

Cancer cells

Tumor Antigens

what is a * Overexpressed Cellular Proteins

A

Overexpressed Cellular Proteins
– Expression for longer times or at different locations
– Abnormally high levels of expression

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8
Q

The Immune System & Cancer

Cancer cells

Tumor Antigen

A
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9
Q

The Immune System & Cancer

Cancer cells

Immune surveillance

3 theories: 1909 Paul Erlich

A

1909 - Paul Erlich
– Hypothesis that host defense may
prevent neoplastic cells from developing
into tumors

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10
Q

The Immune System & Cancer

Cancer cells

Immune surveillance

3 theories: 1953 Gross and Foley

A
  • 1953 - Gross & Foley
    – Evidence of tumor stimulated IR
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11
Q

The Immune System & Cancer

Cancer cells

Immune surveillance
3 theories: late 1950’s MacFarlene Burnet

A
  • Late 1950s - MacFarlene Burnet
    – Tumor cell neoantigens induce an IR
    against cancer
    – Immune surveillance theory

**see slide for diagram

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12
Q

The Immune System & Cancer

Cancer cells
Cancer Immunoediting

  • 2002 - Dunn and Schreiber explain
A

Cancer Immunoediting

  • 2002 - Dunn and Schreiber

– Elimination phase
* Tumor cells are killed by NK, CD4+ and CD8+ cells
– Equilibrium phase
* When the immune system is unable to destroy the tumor
– Escape phase
* Appearance of clinically detectable tumors

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13
Q

The Immune System & Cancer

Cancer cells

Immune Surveillance - Elimination
* Innate immune mechanisms

what are they, how does it work?

A

Immune Surveillance - Elimination

  • Innate immune mechanisms

– Neutrophils
* Produce TRAIL (TNF-related apoptosis-inducing ligand)
* Stimulates apoptosis in tumor cells

– NK cells
* Express NKG2D which can bind MICA and MICB on
many tumor cells

**see slide for below diagram

NK cells

  • Failure to express MHC I
  • Expression of
    nonclassical molecules
    (MICA or MICB)
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14
Q

The Immune System & Cancer

Cancer cells

Immune Surveillance - Elimination

Macrophages
How does this work?

A

Macrophages
– Classically activated M1 macrophages can kill many tumor cells
– Possibly recognized by DAMPs from dying tumor cells through
macrophage TLRs
– Activation of macrophages by IFN-γ produced by tumor-specific T
cells
– Production of nitric oxide (NO)

– M2 macrophages have been known to promote tumor growth
through secretion of vascular endothelial growth factor (VEGF)
and TGF-β

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15
Q

The Immune System & Cancer

Cancer cells

Immune Surveillance - Elimination

  • Adaptive immunity mechanisms

3 ways, how do they work?

A
  • Adaptive immunity mechanisms
    – CD8+ T cells
  • Specific for tumor peptides presented on MHC class I can directly
    lyse tumor cells using perforins and granzymes

– CD4+ T cells
* Activated by APCs presenting tumor antigens leading to direct or
indirect destruction of the tumor
* IFNγ produced by CD4+ T cells activates macrophages
– NKT cells
* Recognize antigen presented by non-classical MHC class I
molecules on tumor cells

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16
Q

The Immune System & Cancer

Cancer cells

Immune Surveillance - Elimination

  • Adaptive immunity mechanisms

How do these work (2 ways)

A

– Tumor-bearing hosts may produce antibodies against
various tumor antigens

– Antibodies may kill tumor cells by activating complement
or by antibody-dependent cell-mediated cytotoxicity

17
Q

The Immune System & Cancer

Cancer cells

what is equilibrium?

A
  • State in which tumor cells
    remain but do not progress
  • Tumor cells are not completely
    eliminated, but neither do they
    proliferate
18
Q

The Immune System & Cancer

Cancer cells
Tumor Escape
4 steps what are they? Explain?

A
  • TGF-β
  • Induces tumor cell proliferation and
    angiogenesis
  • Suppresses elements of the host
    antitumor immune response
  • Indoleamine2,3-dioxygenase (IDO)
  • Suppresses T-cell proliferation
  • Galectin-1
  • Stimulates angiogenesis
  • Programmed cell death ligand 1 (PDL1)
  • Slow down immune responses
19
Q

The Immune System & Cancer

Cancer cells
Tumor Escape

what is: * TGF-β

A
  • TGF-β
  • Induces tumor cell proliferation and
    angiogenesis
  • Suppresses elements of the host
    antitumor immune response
20
Q

The Immune System & Cancer

Cancer cells
Tumor Escape

what is: * Indoleamine2,3-dioxygenase (IDO)

A
  • Indoleamine2,3-dioxygenase (IDO)
  • Suppresses T-cell proliferation
21
Q

The Immune System & Cancer

Cancer cells
Tumor Escape

what is: * * Galectin-1

A
  • Galectin-1
  • Stimulates angiogenesis
22
Q

The Immune System & Cancer

Cancer cells
Tumor Escape

what is: ** Programmed cell death ligand 1 (PDL1)

A
  • Programmed cell death ligand 1 (PDL1)
  • Slow down immune responses
23
Q

The Immune System & Cancer

Cancer cells
Tumor-associated Macrophages

M2 Macrophages explain

A

Tumor-associated Macrophages

17

M2 Macrophages
Can generate an
anti-inflammatory environment

within the tumor

**see diagram

24
Q

The Immune System & Cancer

Cancer cells
Immunological Escape Mechanisms

explain what the 4 features and how they work

A

Immunological Escape Mechanisms

  • Highly similar to self
    – No PAMPs
  • Not all cells will express the same neoepitopes
  • Switch off T-cell responses
    – IL-10 or TGFβ
  • T-cell checkpoint molecules
    – CTLA-4, PD-L1
    – Anergy
25
Q

The Immune System & Cancer

Cancer cells

what do transformed cells frequently do?

A

Transformed cells frequently downregulate molecules that can facilitate T-cell or NK-mediated
attack (e.g., loss of MHC molecules or Tc epitopes, loss of ICAM-1) or upregulate/secrete
molecules that can kill lymphocytes (e.g., FasL) or that can anergize T-cells that infiltrate the tumor
(e.g., PD-L1, PD-L2, IL-10, IDO).

**see diagram

26
Q

The Immune System & Cancer

Cancer cells

Tumor Immunotherapy

2 kinds name them

A
  • Passive immunization
  • Active immunization
27
Q

The Immune System & Cancer

Cancer cells

Tumor Immunotherapy

what is passive immunology

A
  • Passive immunization
    – Nonspecific immune stimulation
  • Cytokine therapy
  • T-cell therapy
    – Monoclonal Ab against tumoral Ag
28
Q

The Immune System & Cancer

Cancer cells

Tumor Immunotherapy

what is passive immunotherapy

A
29
Q

The Immune System & Cancer

Cancer cells

Tumor Immunotherapy

what is active immunotherapy

A
  • Active immunization
    – Chemically modified tumor cells
    – Vaccination against oncogenic
    viruses
  • FeLV, Marek’s disease

Immuno (13 decks)

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