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DWT exam 4 > tumor immunology > Flashcards

tumor immunology Flashcards

1
Q

Tumor Associated Antigens

A

Distinguish neoplastic cells from normal cells
Examples
* Altered proteins due to genetic mutations
* Excessive production of normal proteins
* Viral proteins (if tumor was caused by a virus)
* Expression of proteins not typical for the cell type (de-repression)

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2
Q

Natural Killer cells

A

Part of the innate immune system
Activated by an imbalance between stimulatory and inhibitory signals
* Foreign antigens = stimulatory signal
* Loss of self MHC I = loss of inhibitory signal

Activation – release of cytoplasmic granules that cause cell lysis (Perforin, Granzyme)
Also secrete IFN-gamma which has direct and indirect anti-tumor activities

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3
Q

adaptive immune response to tumors

A

Antigen presenting cells stimulate CD4 Th1
CD4+ Th1 cells Release IFN g to stim CD8+ Tc cells

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4
Q

Stages of immune response to tumor

A
  1. Elimination: All abnormal cells are destroyed
  2. Equilibrium: Cells resistant to immune response = cells destroyed
  3. Escape: Cells resistant to immune response > cells destroyed
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5
Q

Mechanisms of tumor immune system invasion

A

Decreased expression of tumor antigens
Decreased expression of MHC proteins
Decreased co-stimulatory signals

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6
Q

lymphocyte neoplasia

A

lymphoma

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7
Q

plasma cell neoplasia

A

plasma cell tumor

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8
Q

macrophage/APC neoplasia

A

cutaneous histiocytoma

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9
Q

myeloblast neoplasia

A

myeloid leukemia

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10
Q

mast cell tumors

A
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11
Q

Canine Cutaneous Histiocytoma

A

Tumor derived from dendritic cells (APCs)
Common on head, ears, muzzle and legs of young dogs
Characterized by tumor-infiltrating Tc cells
Often spontaneously regress

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12
Q

Inflammation-Associated Neoplasia

A

Mechanisms
* Inflammatory mediators damage DNA
* Inflammation can inhibit apoptosis
* Effects of tumor associated macrophages and regulatory T cells

Examples
* Inflammatory bowel disease and alimentary lymphoma in dogs and cats
* Vaccine-associated sarcoma in cats

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13
Q

Inflammation-Associated Neoplasia

A

Mechanisms
* Inflammatory mediators damage DNA
* Inflammation can inhibit apoptosis
* Effects of tumor associated macrophages and regulatory T cells

Examples
* Inflammatory bowel disease and alimentary lymphoma in dogs and cats
* Vaccine-associated sarcoma in cats

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14
Q

Pro tumor effects of immune system

A

Tumor-associated macrophages
* Infiltrate tumors
* Secrete factor that can promote tumor growth and metastasis
* Metalloproteinases – enzymes that degrade extracellular matrix
* Vascular endothelial growth factor – promotes vessel growth
* IL-10 – immunosuppressive cytokine

Regulatory T cells
* Inhibit NK and Tc cells

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15
Q

Paraneoplastic Syndromes

A

Definition – remote or systemic changes associated with a neoplasm
May be the first indication of cancer
Usually secondary to products of tumor or immune system cells
Most common in veterinary medicine:
* Hypercalcemia
* Hypoglycemia
* Anemia
* Cachexia

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16
Q

Paraneoplastic hypercalcemia

A

Cancer is the most common cause of hypercalcemia in companion animals
* Anal sac apocrine gland adenocarcinoma – tumor produces parathyroid hormone related peptide
* T-cell lymphoma - osteolysis
* Also, multiple myeloma, thyroid carcinoma, osteolytic bone tumors

17
Q

Paraneoplastic Hypoglycemia

A

Glucose utilization by neoplastic cells
Decreased glycogenolysis and gluconeogenesis
Production of insulin-like growth factor

Tumor types
* Insulinoma – excess insulin production
* Hepatocellular carcinoma
* Hemangiosarcoma
* Melanoma
* Lymphoma
* Multiple myeloma

18
Q

Paraneoplastic Anemia

A

Anemia of chronic disease – decreased iron metabolism and storage
IMHA – Cross reaction between tumor antibodies and erythrocyte surface antigens
Blood-loss anemia – gastrointestinal/urinary tumors, hemangiosarcoma
Bone marrow disease – lymphoma or leukemia replacing hematopoietic cells in the bone marrow
Kidney Tumor: decreased EPO

19
Q

Cancer Cachexia

A

Progressive wasting with loss of skeletal muscle and adipose tissue (mostly skel muscle)
Not completely explained by decreased food consumption
50% of cancer patients
Tumors of gastrointestinal tract and lung
Multifactorial
Inflammatory cytokines are an important component
* TNF alpha
* IL-1
* IL-6

20
Q

Cancer Treatment

A

Surgery – remove the tumor
Chemotherapy – disrupt cell division or target tumor cells with chemicals
Radiotherapy – disrupt cell division with radiation
Immunotherapy:
* Tumor non-specific – promote innate immune response
* Tumor specific – promote adaptive immune response

21
Q

Tumor Non-Specific Immunotherapy

A

Macrophage and monocyte activators
* Pattern recognition receptor agonists (MTP for canine osteosarcoma)
* Intratumoral injection of antigens (Immunocidin for mammary tumors in dogs, Acemannan)

NK cell targeted therapy
* Cationic liposome-DNA complexes
* Recombinant cytokines (IFN alpha, IFN gamma, IL-12)

22
Q

Manipulation of Tumor Microenvironment for treatment

A

Microenvironment = fibroblasts, endothelial cells, macrophages
Depletion of tumor associated macrophages
* Liposomal clodronate – in trials for sarcomas in dogs

Inhibition of macrophage migration into tumors
* Migration mediated by chemokine CCL2 binding to CCR2 receptor
* Block with CCR2 agonists

23
Q

Tumor Vaccines

A

Vaccine types
* Whole tumor cells – lysed or irradiated (expensive, no mass production)
* Tumor antigen-specific vaccines (may select for cells that have lost the antigen)

One vaccine currently approved: Tyrosinase protein for melanoma in dogs (Oncept)

Obstacles
* Tumor associated macrophages suppress T cell response
* Regulatory T cells suppress T cell response
* Solution: Vaccine + TAM or Treg depletion

DONT know specifics

24
Q

Adaptive Transfer of Modified T Cells

A

Collect patient’s CD8+ Tc cells (lymph node excision)
Expand the number in culture
Manipulate T cell to target the tumor
Transfect with genes for antibody receptor
Use bi-specific antibodies (bind tumor antigen and T cell)
Re-infuse the lymphocytes

25
Q

Checkpoint Molecule Inhibitors

A

Checkpoint molecules – cell surface molecules that limit T cell proliferation (CTLA-4, PD-1, TIM3, Lag3) when bound to ligands
Blocking these molecules allows for more T cell production
Block with monoclonal antibodies

DWT exam 4 (10 decks)

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