Tumor microenvironment, immunity, and paraneoplastic effects - Exam 4

Parenchyma

Actual tumor cells

Stroma

-Extracellular matrix of tumor

-Contain blood vessels, fibroblasts, and inflammatory/immune cells

Tumor-stromal interactions

Tumor can interact with stroma through signaling molecules (ex. growth factors)

Platelet-derived growth factor (PDGF)

-Released by tumor cells

-Stimulates tumor associated fibroblasts to increase collagen production

Angiogenesis

Creation of new blood vessels

Angiogenic switch

Allows tumor cells to induce and sustain new tumor vasculature

What two growth factors do angiogenic factors include?

-Vascular endothelial growth factor (VEGF)

-Fibroblast growth factor (FGF)

How do tumor blood vessels compare to normal blood vessels?

-More dilated and permeable (leaky)

-Irregularly shaped

-Disorganized

-Abnormal structure and function

What does tumor vasculature allow for?

-Supply nutrients

-Formation of collagenous tumor from leaky vessels

-Allows tumors to metastasize

Lymphangiogenesis

-Creation of lymphatic vessels

-Very similar to angiogenesis

How does inflammation play a role in cancer?

-Inflammatory cells attracted to tumors but do not protect against them

-Chronic inflammation can increase risk of cancer

Immunosurvaillence

-Immune system directed towards self antigens on tumor cells

-Suppresses tumor development

Tumor antigens

Proteins, glycoproteins, glycolipids or carbs expressed on the surface of tumor cells

Tumor-specific antigens

Present only on tumor cells

Tumor-associated antigens

Present on both tumor and normal cells

Oncofetal antigens

Antigens that are only found only in cancer cells or fetal cells

Tumor-specific shared antigens

-Limited expression in adult tissue

-Expressed by many types of tumor tissue

Differentiation antigens

Expressed only at specific stages of differentiation in normal tissue

What are four methods that a tumor uses to evade the immune response?

1. Altered Major Histocompatibility Complex (MHC) Expression

2. Antigen Masking

3. Tolerance

4. Immunosuppression

Altered Major Histocompatibility Complex Expression

Tumor cells can downregulate expression of MHC antigens

Antigen masking

Tumor cells lose or mask antigens

Tolerance

Body thinks the tumor is normal tissue and do not create antibodies against it

Immunosuppression

-Secretory products may be immunosuppressive

-Can produce Fas ligand (triggers apoptosis)

What are two types of immunotherapy?

-Active

-Passive

Passive immunotherapy

Give the patients mature effector cells or antibodies to destroy tumors

Active immunotherapy

Stimulate immune system to fight off response

Paraneoplastic effects

Indirect effects caused by tumor cell products

Why is recognition of paraneoplastic effects important?

-Can facilitate early tumor diagnosis

-Treat symptoms to manage cancer

-Severity may determine tumor grade

What are six categories of paraneoplastic effects?

-Systemic

-Endocrine

-Skeletal

-Vascular/hematopoietic

-Neurologic

-Cutaneous

What are two systemic paraneoplastic effects?

-Anorexia/cachexia

-Fever

Cachexia

Loss of muscle and fat

Endocrine tumors

-Tumor overproduces a hormone

-Can occur with benign or malignant tumors

Nonendocrine tumors

-Ectopic hormone production

-Hormone can be identical, a modified form, or the product of a gene that encodes a protein similar to hormone

What is a type of skeletal syndrome?

Hypertrophic osteopathy

Hypertrophic osteopathy

-Thoracic cancer

-Creates extensive new bone growth (especially on extremities)

What are three kinds of vascular/hematologic syndromes?

-Anemia

-Polycythemia

-Thrombocytopenia

Anemia

Low red blood cell count

Polycythemia

Abnormally high red blood cell count

Thrombocytopenia

Low platelet count

Nodular dermatofibrosis

-Cutaneous syndrome

-Heritable disorder in German Shepherds

-Appears as multiple fibrous nodules in the skin

-Associated with bilateral renal cystadenocarcinomas