Chapter 6: Tumor immunology and neoplasia
Tumor immunology:
Tumor cells express tumor antigens, causing activation immune system so that cancer can be
prevented. A tumor antigen can arise from different groups of proteins:
1. Mutated oncogenes: main cause of transformation of cancer cell
2. Mutated self-antigens: generate changes in the proteins
3. Aberrantly expressed proteins: overexpressed proteins or normally not expressed
4. Oncogenic viral antigens: express viral proteins
Tumor cells can avoid elimination of the immune system by:
- Low immunogenicity = not express neo-antigens or co-stimulatory
- Loss of MHC class 1 molecule, makes the tumor invisible
- Immune suppression, secrete molecules that inhibit the activity of immune cells
- Tumor cells inhibit immune check point
Immune checkpoints = inhibitory pathway to maintain self-tolerance. PD1 and CTLA4 are current
targets in immunotherapy for cancer treatment.
With no therapy > the CTL does not get activated because inhibiting receptor is bound
With therapy > antibody binds to CTL inhibitory receptor, causing CTL to become active and attack
tumor cell. Possible side effect is auto-immune reactions.
CAR T cell therapy = take T cell, modify to become toxic for the tumor cell and insert it. Possible side
effect is the cytokine storm.
Neoplasia:
Benign: well differentiated, slow growing, non-invasive and nonmetastatic
Malignant: poorly differentiated, rapid growing, locally invasive and metastic.
Terminology:
Cell type benign malignant
Glandular epithelium adenoma adenocarcinoma
Squamous epithelium papilloma squamous cell carcinoma
Fat tissue lipoma liposarcoma
Melanocyte naevus melanoma
General characteristics of malignant tumors: loss of differentiation (anaplasia), pleomorphism
(multiplicity), disorderly architecture and abnormal mitotic activity.
Cancer causing factors:
Environmental factors are involved in cancer development: chemical (cigarettes, alcohol), physical
(UV, X-ray) and viruses (HPV).
Cancer is a DNA disease:
- Chemical and physical factors that can cause cancer act via damaging DNA. Can cause
different pairs (DNA mutations) of nucleotides after UV radiation
- Specific chromosomal abnormalities are associated with cancer, a gain, loss of translocation
These both genetic changes are irreversible. When the structure of the DNA sequence is altered, like
DNA methylation, this also can cause cancer. But this is a reversible event.
When DNA changes provide a growth benefit they are retained, and a tumor can arise.
Oncogenes:
Gas paddle for cell proliferation. When activated/mutated the paddle become stuck and constant
active. This is a dominant effect, so only one chromosome could have it.
Proto-oncogenes have the function:
Tumor immunology:
Tumor cells express tumor antigens, causing activation immune system so that cancer can be
prevented. A tumor antigen can arise from different groups of proteins:
1. Mutated oncogenes: main cause of transformation of cancer cell
2. Mutated self-antigens: generate changes in the proteins
3. Aberrantly expressed proteins: overexpressed proteins or normally not expressed
4. Oncogenic viral antigens: express viral proteins
Tumor cells can avoid elimination of the immune system by:
- Low immunogenicity = not express neo-antigens or co-stimulatory
- Loss of MHC class 1 molecule, makes the tumor invisible
- Immune suppression, secrete molecules that inhibit the activity of immune cells
- Tumor cells inhibit immune check point
Immune checkpoints = inhibitory pathway to maintain self-tolerance. PD1 and CTLA4 are current
targets in immunotherapy for cancer treatment.
With no therapy > the CTL does not get activated because inhibiting receptor is bound
With therapy > antibody binds to CTL inhibitory receptor, causing CTL to become active and attack
tumor cell. Possible side effect is auto-immune reactions.
CAR T cell therapy = take T cell, modify to become toxic for the tumor cell and insert it. Possible side
effect is the cytokine storm.
Neoplasia:
Benign: well differentiated, slow growing, non-invasive and nonmetastatic
Malignant: poorly differentiated, rapid growing, locally invasive and metastic.
Terminology:
Cell type benign malignant
Glandular epithelium adenoma adenocarcinoma
Squamous epithelium papilloma squamous cell carcinoma
Fat tissue lipoma liposarcoma
Melanocyte naevus melanoma
General characteristics of malignant tumors: loss of differentiation (anaplasia), pleomorphism
(multiplicity), disorderly architecture and abnormal mitotic activity.
Cancer causing factors:
Environmental factors are involved in cancer development: chemical (cigarettes, alcohol), physical
(UV, X-ray) and viruses (HPV).
Cancer is a DNA disease:
- Chemical and physical factors that can cause cancer act via damaging DNA. Can cause
different pairs (DNA mutations) of nucleotides after UV radiation
- Specific chromosomal abnormalities are associated with cancer, a gain, loss of translocation
These both genetic changes are irreversible. When the structure of the DNA sequence is altered, like
DNA methylation, this also can cause cancer. But this is a reversible event.
When DNA changes provide a growth benefit they are retained, and a tumor can arise.
Oncogenes:
Gas paddle for cell proliferation. When activated/mutated the paddle become stuck and constant
active. This is a dominant effect, so only one chromosome could have it.
Proto-oncogenes have the function:
