INC TUMOR IMMUNOLOGY

Tumor immunology

studies the interaction between the immune system and cancer cells

It covers tumor antigens, immune responses,

immune evasion and immunotherapy

Abnormal cell mass that developed due to

excessive cell growth and division

Benign tumors

Slowly growing cells that are similar to the normal tissue which they originated (encapsulated). Slowly growing cells that have the same characteristics as the normal cells of tissues but abnormally bigger. Also well-differentiated

Cancers/Malignant tumors

invasive, disorganized and can metastasize

Rarely encapsulated

Carcinomas

• 80% of malignant tumors

• Derived from epithelial cells

• Ex: internal organ lining, glands, skin

Leukemias/Lymphomas

• 9% of malignant tumors

• Derived from bone or soft tissues such as fat, muscles, tendons, cartilage, nerves, and blood vessels.

CARCINOGENESIS

• Refers to the transformation of normal cells Into malignant cells.

• Multistep process involving a series of genetic mutations that cause the phenotype of a cell to be changed over time

Factors:

1. Chemical Carcinogens

2. Radiation

3. Viruses

Proto-oncogenes

Gene involved in cancer/maglinant transformation: normal genes promoting cell growth; mutations convert them into oncogenes

Tumor suppressor genes

inhibit cell cycle or induce apoptosis; mutations cause loss of control and DNA repair failure

• Inhibit excessive cell division

• Recognize and repair damaged DNA

• FX: to prevent newer cells to generated

Antigens recognized by immune system as foreign, some are only found in tumor cells.

• “tumor markers”

• Tumor immunology relies on the idea that tumor cells express antigens recognized by the immune system

  These antigens may be unique to tumors (tumor-specific antigens) or shared with normal cells (tumor-associated antigens)

Neoantigens/Mutation Tumor Antigens/MTAs

• Arise from genetic mutations in proto-oncogenes, tumor suppressor genes or other genes

• Presented on MHC I molecules to T cells, triggering anti-tumor responses

• “Tumor Specific Antigens”

EBV antigens in B-cell lymphomas

• Examples of viral antigens found in tumors caused by oncogenic viruses

• Processed and presented via MHC I pathway

CANCER / TESTIS ANTIGENS

Normally found in testes, ovaries and placenta but

not in somatic cells

Re-expressed in cancers of other origins

Example:

○

MAGE proteins in melanoma

CEA/Carcinoembryonic protein

AFP/Alpha-fetoprotein

PSA/Prostate-Specific Antigen

CALLA/Common Acute/CD10

Lymphoblastic Leukemia Antigen

DIFFERENTIATION ANTIGENS Expressed during early cell development,

especially in immune cells

Include oncofetal antigens re-expressed in tumors

Human Epidermal Growth

Factor Receptor 2 protein/HER2 protein

Overexpressed Antigens

● Found in higher levels on malignant cells than on normal cells.

• In certain breast cancers and targeted in therapy

CA 125

Ovarian cancer antigen marker

CA 19-9

pancreatic and gastro intestinal cancer

Prognosis

predicting disease aggressiveness and

treatment suitability

Monitoring

assessing treatment response and

detecting recurrence

CA 125, CA15-3, CA19-9

Enumerate carbohydrate antigens

Carcinoembryonic Antigen (CEA)

Most widely used marker for colorectal

cancer

Main application is for monitoring patients

undergoing therapy for Colorectal Cancer

Alpha Fetoprotein (AFP)

An oncofetal antigen

○

Synthesized by the fetal liver and yolk

sac, and is abundant in fetal serum

Most widely used tumor marker for

Hepatocellular Carcinoma

Tumor marker for nonseminomatous germ

cell cancers of the testes

AFP declines to low levels (10-20 ug/L) by 12

months of age. (Habang lumalaki yung

person, dapat bumababa siya).

Human Chorionic Gonadotropin (hCG)

Pregnancy hormone

Type: Glycoprotein (45,000 MW), composed of α

and β subunits

Cancer use: Marker for testicular and ovarian germ

cell tumors and choriocarcinoma

Clinical uses: Diagnosis, prognosis, monitoring

therapy, detecting relapse

Testing considerations: Multiple forms measured

(intact hCG, β subunit, fragments); rising trends

more reliable than single values

Other elevations: Pregnancy, gonadal suppression

from chemo, testicular dysfunction

Most widely used marker for Prostate

Cancer

Type: Glycoprotein (28,000 MW), specific to

prostate tissue

Cancer use: Marker for prostate cancer

Clinical uses:

○

Screening (with caution)

○

Differential diagnosis between BPH, weak

and aggressive prostate cancers

○

Monitoring treatment and detecting

recurrence

Screening debate:

○

Not cancer-specific: also elevated in BPH,

prostatitis, recent ejaculation or prostate

exams

○

May lead to overdiagnosis and

overtreatment

○

Screening most beneficial for men aged

55-69

Test improvements:

○

Free PSA vs. total PSA ratio

○

PSA velocity (PSAV): >0.75 ng/mL/year

suggests cancer

○

PSA density (PSAD): PSA value relative to

prostate volume

○

PCA3 RNA testing in urine adds diagnostiC value

Post treatment use: ○

Rising PSA after surgery = recurrence

○

Slow PSA decline after radiation = limitation

PSA doubling time can reflect tumor aggressiveness