Lecture 11 Immunology Tumor immunology Dr: Dalia Galal.

Lecture 11 ImmunologyLecture 11 Immunology

Tumor immunologyTumor immunology

Dr: Dalia Galal

Tumor Tumor Cells that continue to

replicate, fail to differentiate into specialized cells, and become immortal.

1. Malignant: A tumor that grows indefinitely and spreads (metastasis)--also called cancer: kills host

2. Benign: A tumor that is not capable of metastasis: does not kill host

muscle, nerve, bone, blood

Types of CancerTypes of Cancer Carcinoma: arising from epithelial tissue, such as

glands, breast, skin, and linings of the urogenital, digestive, and respiratory systems (89.3% of all cancers)

Sarcoma: solid tumors of muscles, bone, and cartilage that arise from the embryological mesoderm (1.9% of all cancers)

Leukemia: disease of bone marrow causing excessive production of leukocytes (3.4% of all cancers)

Lymphoma, Myeloma: diseases of the lymph nodes and spleen that cause excessive production of lymphocytes (5.4% of cancers)

Tumor immunologyTumor immunology

* Transformation of normal cells to malignant cells by:* Transformation of normal cells to malignant cells by: a- a- Spontaneous mutationSpontaneous mutation during daily cell division during daily cell division chemical carcinogenschemical carcinogens b- It may be b- It may be induced byinduced by physical carcinogens physical carcinogens virusesviruses

* Cells become * Cells become antigenically differentantigenically different from normal cells from normal cells

* They are * They are recognizedrecognized and and destroyeddestroyed by by immune systemimmune system

Etiology Of TumorEtiology Of Tumor1) Inherited :1) Inherited : Expression of inherited oncogene Expression of inherited oncogene e.g. viral gene incorporated into host genee.g. viral gene incorporated into host gene

2) Viral:2) Viral: - Human papilloma, herpes type 2, HBV, EBV (DNA)- Human papilloma, herpes type 2, HBV, EBV (DNA) - Human T-cell leuckemia virus (RNA)- Human T-cell leuckemia virus (RNA)

3) Chemical:3) Chemical: - Poly cyclic hydrocarbons cause sarcomas- Poly cyclic hydrocarbons cause sarcomas - Aromatic amines cause mammary carcinoma - Aromatic amines cause mammary carcinoma - Alkyl nitroso amines cause hepatoma- Alkyl nitroso amines cause hepatoma

4) Radiological:4) Radiological: Ultraviolet & ionizing irradiation Ultraviolet & ionizing irradiation

5) Spontaneous:5) Spontaneous: failure in the cellular growth control failure in the cellular growth control

Types of Tumor Associated Types of Tumor Associated AntigensAntigens

1) Viral Antigen :1) Viral Antigen : a- Viral proteins and glycoproteinsa- Viral proteins and glycoproteins b- New antigens produced by virally infected host b- New antigens produced by virally infected host cells under control of viral nucleic acid cells under control of viral nucleic acid

2) Tumor specific antigens :2) Tumor specific antigens : - Tumor cells develop new antigen specific to - Tumor cells develop new antigen specific to their carcinogenstheir carcinogens

3) Tumor specific transplantation antigens :3) Tumor specific transplantation antigens : - Tumor cells express new MHC antigens due to - Tumor cells express new MHC antigens due to alteration of normally present MHC antigensalteration of normally present MHC antigens

Tumor Associated AntigensTumor Associated Antigens

4) 4) Oncofetal antigens:Oncofetal antigens:

a- Carcino-embryonic antigens (CEA)a- Carcino-embryonic antigens (CEA) - Normally expressed during fetal life on fetal gut- Normally expressed during fetal life on fetal gut - Reappearance in adult life: - Reappearance in adult life: GIT, pancreas, biliary system and cancer breastGIT, pancreas, biliary system and cancer breast

b- Alpha fetoprotein:b- Alpha fetoprotein: - Normally expressed in fetal life - Normally expressed in fetal life - Reappearance in adult life; hepatoma- Reappearance in adult life; hepatoma

Immune Surveillance SystemImmune Surveillance System This system include :This system include : 1) Natural killer (NK) cells1) Natural killer (NK) cells They kill directly tumor cells,helped by interferon, IL-2They kill directly tumor cells,helped by interferon, IL-2

2) Cytotoxic T-cells2) Cytotoxic T-cells They also kill directly tumor cellsThey also kill directly tumor cells

3) Cell mediated T-cells (effector T-cells)3) Cell mediated T-cells (effector T-cells) They produce and release a variety of lymphokines : They produce and release a variety of lymphokines : a-Macrophage activation factora-Macrophage activation factor that activate macrophag that activate macrophag b-b-γγ interferon and IL-2 interferon and IL-2 that activate NK that activate NK c-Tumor necrosis factor (TNF) c-Tumor necrosis factor (TNF)

Immune Surveillance SystemImmune Surveillance System4) B-cells 4) B-cells :: - Tumor associated antigens stimulate production of - Tumor associated antigens stimulate production of specific antibodies by host B-cellsspecific antibodies by host B-cells

- These specific antibodies bind together on tumor cell surface - These specific antibodies bind together on tumor cell surface leading to destruction of tumor through:leading to destruction of tumor through:

a- Antibody mediated-cytotoxicity :a- Antibody mediated-cytotoxicity : killkill Cytotoxic T-cells IgG-coated tumor cellsCytotoxic T-cells IgG-coated tumor cells

b- Activation of macrophagesb- Activation of macrophages releaserelease Sensitized T-cells macrophage activating factorSensitized T-cells macrophage activating factor IgG-coated tumor cells macrophages IgG-coated tumor cells macrophages activateactivate

c- Activation of classical pathway of complementc- Activation of classical pathway of complement leading toleading to Lysis of tumor cellsLysis of tumor cells

Tumor EscapeTumor EscapeMechanisms by which tumor escape immune defenses:Mechanisms by which tumor escape immune defenses:

1) Reduced levels or absence of MHCI molecule1) Reduced levels or absence of MHCI molecule on tumor so that they can on tumor so that they can not be recognized by CTLs not be recognized by CTLs

2) Some tumors stop expressing the antigens2) Some tumors stop expressing the antigens These tumors are called “antigen loss variants”These tumors are called “antigen loss variants”

3) Production of immunosuppressive factors by tumor3) Production of immunosuppressive factors by tumor e.g. transforming e.g. transforming growth factor (TGF-growth factor (TGF-ββ))

Tumor cells have an inherent defect in antigen processing and Tumor cells have an inherent defect in antigen processing and presentation presentation

5) Blocking of receptors on T-cells by specific antigen antibodies complex5) Blocking of receptors on T-cells by specific antigen antibodies complex

6) Antigens on the surface of tumors may be masked6) Antigens on the surface of tumors may be masked by sialic acid by sialic acid

Tumor MarkersTumor Markers* They are either * They are either Tumor antigens Tumor antigens or or Tumor productsTumor products1- Tumor Antigens1- Tumor Antigens 1) Alpha fetoprotein antigen (AFP)1) Alpha fetoprotein antigen (AFP) in cases of hepatoma in cases of hepatoma

2) Carcinoembryoinic antigen (CEA)2) Carcinoembryoinic antigen (CEA) in gastrointestinal in gastrointestinal tumors, tumors of biliary system and cancer breasttumors, tumors of biliary system and cancer breast

3) Cancer antigen 1253) Cancer antigen 125 (CA 125)(CA 125) in ovarian carcinoma in ovarian carcinoma

4) Cancer antigen 15-3 (CA15-3)4) Cancer antigen 15-3 (CA15-3) in breast cancer in breast cancer

5) Cancer antigen 19-95) Cancer antigen 19-9 in colon and pancreatic tumor in colon and pancreatic tumor

6) Prostatic specific antigen (PSA)6) Prostatic specific antigen (PSA) in prostatic tumors in prostatic tumors

2- Tumor Products2- Tumor Products a) Hormones :a) Hormones : -- Human chorionic gonadotrophins (HCG)Human chorionic gonadotrophins (HCG) are secreted are secreted

in cases of choriocarcinomain cases of choriocarcinoma - Thyroxin (T3 & T4)- Thyroxin (T3 & T4) is secreted in cases of cancer is secreted in cases of cancer of thyroid glandof thyroid gland

b) Enzymes :b) Enzymes : - Acid phosphatase- Acid phosphatase enzymes in cases of cancer prostae enzymes in cases of cancer prostae - Alkaline phosphatese, lipase and amylase- Alkaline phosphatese, lipase and amylase enzymes in enzymes in

cases of cancer pancreascases of cancer pancreas