Tumor Immunology

Dr.Marián Sabol, PhD.

P.J. Šafárik University, Medical Faculty, Institute of Medical MicrobiologyTr. SNP 1, Košice, Slovakia

IntroductionIntroduction

Current estimates project that one person in three will develop cancer and one person in five will die from cancer.

(J.Kuby, 1992)

Immunologic perspective

Cancer cells can be viewed as altered self cells that have escaped normal growth-regulating mechanisms.

The scope of lecture

1) Unique properties of cancer cells

2) Immune responses that develop to cancer cells

3) Escape of cancer cells

4) Therapies: clinical and experimental

Origin of CancerOrigin of Cancer

-Cell growth regulation-Balance: cell renewal – cell death-Lifespan of cells

-Cancer (tumor, neoplasm) -Cells which are no responsive to growth-

control mechanisms

-Clones that can expand to a considerable size

(or number)

Malignant transformationMalignant transformation

NNormal cellsormal cells Transformed cellsTransformed cells

Proto-oncogenesProto-oncogenes

Viral-oncogenesViral-oncogenes

CellularCellular-oncogenes-oncogenes

retroviral transductionretroviral transduction

mutagens, radiation, viruses,mutagens, radiation, viruses, growth controlling proteinsgrowth controlling proteins -growth factors-growth factors -GFR-GFR -signal transducers-signal transducers - intranuclear factors- intranuclear factors

Malignant transformationMalignant transformation

CMLCMLPhiladelphia chromosome (reciprocal translocation) Philadelphia chromosome (reciprocal translocation)

Terminology Terminology

1) Benign-not capable of indefinite growth-does not invade the surrounding tissue extensively

2) Malignant-tumor that continues to grow-becomes progressively invasive -exhibit metastasis

Metastasis

Terminology Terminology

Classification according embryonic origin of tissue from which tumor is derived

1) Carcinomas-endodermal and ectodermal tissues

(skin, epithelial lining of internal organs and glands)

2) Sarcomas-mesodermal connective tissues

(bone, fat, cartilage)

3) Leukemias and lymphomas-hematopietic cells of bone marrow

Malignant tumorsMalignant tumors

MelanomaMelanoma

Properties of Cancer CellsProperties of Cancer Cells

Cancer cells

1) clonally derived

2) changes in in vivo and in vitro growth

3) altered tissue-specific affinities

4) biochemical changes

5) chromosomal abnormalities

Tumor Antigens

TTumor umor „S„Specificpecific““ Ag Ag

1) 1) MHCI plus abnormal cell proteins (Brc-Alb, Philadelphia chromosome, MHCI plus abnormal cell proteins (Brc-Alb, Philadelphia chromosome, CML)CML)

2) 2) MHCI plus viral proteins(MHCI plus viral proteins(EBV, SV40, polyoma virusEBV, SV40, polyoma virus))3) Abnormal glycosylation3) Abnormal glycosylation4) Idiotypes of myelomas and lymphomas4) Idiotypes of myelomas and lymphomas

Tumor Associated AntigensTumor Associated Antigens

1) Oncofetal Ag (alphafetoprotein – hepatoma, carcinoembryonic Ag – colon ca.)

2) Melanoma Ag (MAGE-1, Melan-A)3) Her/neu Ag (GFR)4) EPCAM (epithelial cell adhesion molecule, carcinomas)5) Differentiaion Ag (CALLA: common acute lymphoblastoid leukemia

antigen CD10 pre-B cells)

Anti-tumor immunity

Anti-tumor immunity involve the Anti-tumor immunity involve the same mechanismssame mechanisms as in as in anti-infection immunity, transplantation immunity or allergy.anti-infection immunity, transplantation immunity or allergy.

•ComplementComplement•LysozymeLysozyme•CytokinesCytokines

•PhagocytosisPhagocytosis•NK cellsNK cells

•AntibodiesAntibodies•Tcells Tcells

Tumor Immunology

Cytotoxic T cells

Cytotoxic T cells

Tumor Immunology

Cancer ImmunotherapyCancer Immunotherapy

1) Immune adjuvans-BCG (Bacillus Calmette Guérin) Mycobacterium bovis

-mph >IL-1>Th, breast tumors, malignant melanoma-Corynebacterium parvum

- DNCB (dinitrochlorobenzene) >>> DTH reaction

Cancer ImmunotherapyCancer Immunotherapy

2) Cytokine therapy-IFN, IL-1, IL-2, IL-3, IL-4, IL-5, GM-CSF, TNF

InterferonsIFN alfa and beta - antiviral state, IFN gamma – activation IFN-alfa >> hematologic malignances, melanoma, renal cancer, breast cancer (low degree of malignity)-increase of tumor cell MHCI and mph MHCII >> CTL activity-IFN gamma >> increase the activity of Tc, NK, mph,

Tumor necrosis factors- TNF alfa and beta > -decrease the proliferation of tumor cells and killing

-decrease the angiogenesis - adverse reactions

_______________Systemic administration of high level of a given cytokine has been shownto lead to serious and even life threatening consequences.

Cancer ImmunotherapyCancer Immunotherapy

TIL and LAK cells

-in vitro Tc activation (X-irradiated tumor cells and IL-2)-activation with IL-2 without tumor cells >> LAK cells

(activated NK, NC cells)-systemic IL-2 >> vascular leak syndrom, shock

Tumor cell Vaccines- autologous tumor cells +BCG- engineered tumor cells which produce cytokines (IL-2, GM-

CSF,..)

Tumor Immunology

Thank you for attention.Thank you for attention.

Tumor Immunology