Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

EXMD 504 > Lecture 8: tumor microenvironment > Flashcards

Lecture 8: tumor microenvironment Flashcards

1
Q

what are the factors that influence survival rates

A

-genetivs
-epigenetivs
-phenotypes
-microenvironment
-clinical response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

which type of cancer accounbds for 90% all cancers and arise from epithelial cells

A

carcinomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

which type of cancer arise from supporting tissues like bone, cartilage, fat and muscle

A

sarcomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what are the 3 main characteristics of cancer

A

-loss of growth control
-local invasion
-altered tissue organozation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what are the 3 corollaries of smt (somatic mutation theory)

A

-mutations are necessary for cancer to arise
-mutations make founder cell unable to control its proliferation= tumor formation
-cancer is irrevercible
-this implies that cancer is a cellular disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

are mutations sufficient for cancer devlopment

A

maybe not

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

true or false: epithelial tissues are typically highly proliferative

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

true or false: epithelial tissues are often maintained by stem and progenitor pops

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

carcinboma frequently devlop fronm what

A

pre malignat stages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

tumor incidence is determined by what

A

life long generative capacity of mutated cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

tissues subject ti what generally exhibit high cancer incidence

A

chronic inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

hepatocellular cancer is the leading cause of what

A

death in patients with liver cirrhosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

which type of cancer is associated with IBS

A

colorectal cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

stromal cells accumulate and become activated, creating….

A

pro tumorigenic niche

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

true or false, systematic inflammation is always pro cancer

A

false it can also fuck uop some cancers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

predicted cancer incidence of lung, gastrointestinal, reproductive and skin cancers is higher in ….

A

immunosupressed organ transplant recipients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

which cancer has a reduced incidence in transplant recipients

A

breast cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Possible mechanisms for spontaneous regression

A
  • Silencing oncogenes/activating tumour suppressors
  • Epigenetic mechanisms
  • Tumor inhibition by growth factors and/or cytokines
  • Induction of differentiation
  • Hormonal mediation
  • Elimination of a carcinogen
  • Tumor necrosis or apoptosis
  • Angiogenesis inhibition
  • Immune mediation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what are the 3 corollaries of TOFT are

A
  1. Mutations lead to cancer by disrupting morphostats.
  2. Mutations that induce proliferation are not needed for
    carcinogenesis;
  3. Genetic instability is a byproduct of carcinogenesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

true or false: according to toft, carcinogenesis is not reversible

A

false, it is

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what is edac

A

-epithelial defense against cancer
-intrinsic ability of normal epithelial cells to supress or eliminate adjacent tumor cells
-ex: apoptosis, senescence, cell competition against more and less fit cells, apical extrusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what is apical extrusion

A

-cells know the mechanical difference between normal and cancer cells, apical extrusion is when the cells go to die in the lumen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

systemic signaling can modify what

A

the tumor microenvironment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

systemic signaling in obese tissues

A

-aligned collagen
-increased stiffness
-hypoxic
-pro-inflammatory state

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

systemic signaling in lean tissue

A

-less aligned ecm
-lower stiffness
-normotoxic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

competition results in ….

A

senescence of damages cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

cell competition that selects for the least damaged cells,is controlled by what?

A

-competition is controlled by p53
-distinct from the classical p53 mediated dna damage response
-depends on the relative rather than absolute level of p53 in competing cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

the cell competition is mediated by what

A

-by non cell autonomous induction of growth arrest and senescence related gene expression in outcompeted cells with higher p53 activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

in which breast cancer stage does myoepithelial cells breakdown

A

stage 0

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

which type of cells dynamically prevent dissemination

A

myoepithelial cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

true or false: many of the hallmarks of cancer events are non cell autonomous

A

true
they depend on the interactions with the microenvironment

32
Q

true or false: camcer is a tissue level disease

A

true

33
Q

stromal phenotype can predict what

A

patient outcome

34
Q

reciprocal; interactions between tumor and associated immune and stromal cell types evolve as……

A

the tumor grows, thus allowing for modulation of both tumor cell intrinsic and extrinsic processes

35
Q

true or false: the stroma and the tumor develop together

A

true

36
Q

true or false: many stromal cells are initially repressive, and become trained by the tumor to be supportive

A

true

37
Q

The inconsistency of CAF
markers/gene signatures, which
represents the heterogeneity of the
stromal compartment and the ample
reservoir for their cell of origin,
suggest ……

A

that the tumor and its
microenvironment exhibit a
considerable degree of plasticity

38
Q

CAFs’ should be defined as …….

A

the
dynamic state of fibroblast-like cells
found in the vicinity of the tumor
that promote its progression – for
brevity a ‘CAF state’.

39
Q

fibbrpblast directly associate with and lead what ?

A

cancer cells during invasion

40
Q

non cellular components of the stroma influence what?

A

epithelial cancer cell behaviors

41
Q

hypoxia influence what

A

tumor progression
-tumor vascularization
-chemo abd radio resistance
-emt
-metastasis

42
Q

dual role of macrophages in cancer

A

-m1: killing tumot cells and antihumor immunity
-tissue remodelling and angiogenesis and tumor progression

43
Q

macrophage polarization

A

-activated at a given point in space and time
-macrophages intergrate multiple signals from microenvironment to control polarization

44
Q

what do tams to in ovarian cancer

A

they promote metastasis

45
Q

EGF secreted by TAMs activates……..

A

EGF secreted by TAMs activates
EGFR on tumor cells, which in turn
upregulate VEGF/VEGFR signaling
in surrounding tumor cells to
support tumor cell proliferation
and migration.

46
Q

MACROPHAGES STIMULATE WHAT

A

invasion and metastasis

47
Q

immunoediting 3 stages

A

-elimination
-equilibrium
-escape

48
Q

elimination

A

Elimination
* Tumour cells that are vulnerable to attack by the immune system are cleared
* cells that have or acquire a capacity to circumvent surveillance can survive and
propagate a new tumor that is primed to evade the immune system

49
Q

equioibrium

A

driven by a strong selective pressure from the adaptive arm of the immune system, including T cells

50
Q

escape

A

-establishing a global immunosuppressive state by secreting a plethora of anti-
inflammatory cytokines
* recruiting immunosuppressive cell types (Treg cells and MDSCs), which further
contribute to the anti-inflammatory cytokine milieu

51
Q

Directing the immunoediting process to remain in the equilibrium phase
could ……

A

synergize with standard-of-care therapy to manage incurable disease and maximize the remission period for patients

52
Q

T cell activity can be modulated by
several factors

A
  • T cell exhaustion, a state in which T cells become less responsive to antigens and are ineffective at providing T cell help or eliminating appropriate targets
  • Immune checkpoint (suppression by cancer and stromal cells)
  • Many cells have suppressive functions in the
    tumour microenvironment (for example,
    neutrophils and Treg cells);
53
Q

hot and cold tumors

A

Immunologically Hot Tumors:

Definition: Immunologically hot tumors are characterized by a high level of immune activity within the tumor microenvironment.
Features:
High levels of pro-inflammatory cytokines.
Generally associated with a better response to immunotherapies, such as immune checkpoint inhibitors.
-pd1 and pdl1 receptors
Immunologically Cold Tumors:

Definition: Immunologically cold tumors have a low level of immune activity within the tumor microenvironment.
Features:
Limited infiltration of immune cells into the tumor.
Low expression of immune checkpoint proteins.
Reduced production of pro-inflammatory cytokines.
Generally associated with a poorer response to immunotherapies.

54
Q

true ort false: stroma is genetically stable compaired to tumor cells

A

true
-less susceptible to classical mechanisms opf therapeutic resistance

55
Q

Limited benefit from therapies aiming to deplete stromal cells

A

 Various angiogenesis inhibitors have had limited benefits
 possibly because they generally block the anti-tumorigenic effects of the microenvironment

56
Q

true or false: eliminating sub-populations of stromal cells may have therapeutic benefit

A

true

57
Q

….. cancer-associated stromal cells may have
therapeutic benefit

A

“Re-educating”

58
Q

immunotherapy

A
  • Improve or induce immunological surveillance recognition and destruction cancer cells
  • Modify or stimulate a patient’s immune system to target cancer cells
59
Q

approaches of immunotherapy

A

-Adoptive cell transfer
 Checkpoint inhibitors
 Monoclonal antibodies (recognize cancer cell-specific
antigen and stimulate immune response)
 Cancer vaccines
 Cytokines (modulate the immune system)

60
Q

Adoptive cell transfer

A

Chimeric antigen receptors are generated to target specific antigens. Patients T cells are
engineered to express the chimeric receptor.

61
Q

n 2017, two CAR T-cell therapies were approved by the FD

A

-one for the treatment of
children with acute lymphoblastic leukemia (ALL)
- for adults with advanced
lymphomas. Designed to recognize CD19 on B-cella

62
Q

CTLA-4 (cytotoxic T lymphocyte–associated
protein 4)

A
  • Inhibits T-cell activity by outcompeting
    costimulatory CD28 for CD80/CD86
  • anti-CTLA-4 - advanced melanoma; other
    cancers in clinical trials
63
Q

PD1 (programmed cell death 1 (PD-1)
receptor) and its ligand PD-L1

A
  • PD-L1 expressed on cells within a tumor
    and inhibits T-cell function
  • Anti-CPDL or anti-PDL1 – melanoma,
    NSCLC, RCC, Bladder, head and neck,
    other cancers
64
Q

immune checkpoint blockade inhibitors

A

-ctla4 and pd1

65
Q

Target cancer cells with monoclonal
antibodies

A
  • Markers differentially expressed between
    normal stem cells and leukemic stem cells
     CD44, the cytokine receptor IL3R, and the
    immunoglobulin mucin TIM-3
  • Treatment with antibodies against these cell
    surface molecules dramatically decreased
    leukemogenicity and eradicated leukemic
    stem cell
     Activates immune system to remove targeted
    cells
66
Q

immunotherapy stimulate what

A

immune destruction of tumors

67
Q

pancreatic cancer stem cells express what

A

high levels of EpCAM on the surface

68
Q

what is mt110

A
  • MT110 – bispecific antibody that recognizes 2
    specific antigens
     1) CD3, lymphocyte marker
     2) EpCAM
69
Q

immunotherapy redirects what

A

cutotoxic cd8 T cells to the primary tumors aka xenographs

70
Q

Tumour-associated macrophages (TAMs) can be reprogrammed pharmacologically to restore their anti- tumour activity

A

 Macrophages depend upon colony stimulating factor (CSF)-1
for differentiation and survival.
 TAMs were not depleted in treated mice.

71
Q

 …..BLZ945, a CSF-1R inhibitor was used to target TAMs in a mouse glioblastoma mode

A

- BLZ945, a CSF-1R inhibitor was used to target TAMs in a
mouse glioblastoma model
* regressed established tumors and patient-derived glioma xenografts
* dramatically increased survival

72
Q

Activated/M2 macrophage markers decreased in …….

A

surviving TAMs, consistent with impaired tumor-promoting functions

73
Q

immunotherapy is working on both immune hot and cold

A

false only hot tumors, aka nmot on cold like prostate camcer

74
Q

Challenges for immunotherapy

A

Some tumors are densely infiltrated by immune cells from the innate
and adaptive immune systems (“immune hot”)
* Some tumors have immune cells restrict immune infiltration (“immune cold

75
Q

New approaches to turn cold into hot tumors being investigated

A

Combination with cytotoxic therapeutics induces apoptosis which can stimulate an
immune response

76
Q
A

EXMD 504 (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions