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Tumor Immunology. Mitzi Nagarkatti, PhD Professor and Chair Dept. of Pathology, Microbiology and Immunology School of Medicine and Deputy Director, Basic and Translational Research University of South Carolina Cancer Center Tel. # (803)733-3275 E-mail: firstname.lastname@example.org.
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Mitzi Nagarkatti, PhD
Professor and Chair
Dept. of Pathology, Microbiology and Immunology
School of Medicine
Deputy Director, Basic and Translational Research
University of South Carolina Cancer Center
Tel. # (803)733-3275
Ags expressed by cancer cells
Nature of immune response
How cancer evades immune system
Control of cell
e.g. Gardasil vaccine – Human Papilloma Virus (HPV) induced cervical cancer
TSTA: unique to a tumor
Play an important role in tumor rejection.
TATA: shared by normal and tumor cells
Tumor-associated developmental Ag (TADA)
Tumor-associated viral Ag (TAVA)
Melanomas and melanocytes express MART-1
MHC Class II
T helper (Th) cell
MHC Class I
Cytotoxic T lymphocyte (CTL)
Class I MHC
molecules involved in T cell activation.
Tumors escape the action of CTL by not expressing B7 which provides 2nd signal involved in T cell activation
When tumor cells express Fas Ligand,
they can kill Fas+ T cells, thereby escaping
Surgery Radiation Chemotherapy
Passive Immunization: Preformed Abs or immune cells transferred
Abs against growth factor receptor e.g. IL-2R in HTLV-1 induced Adult T cell leukemia
Abs specific for oncogene product e.g. Abs against HER2/neu (Herceptin or trastuzumab)
Anti-tumor Abs coupled to toxin, radioisotopes, drugs or enzymes:
Ricin A/diphtheria/Pseudomonas toxin coupled to Abs. e.g. antiCD20-Pseudomonas toxin in B cell leukemia
Internalized toxin inhibits protein synthesis.
Cytocidal isotopes or anticancer drugs (adriamycin) coupled to Abs
1. Lymphokine-activated killer cells (LAK): Peripheral Blood Lymphocyte (PBL) + high dose IL-2
2. Tumor-infiltrating lymphocytes (TIL):
In and around solid tumors
Activated NK and CTL
Isolate lymphocytes from blood
of cancer nodule
Successful treatment of melanoma and renal cell carcinoma
1. Interleukin -2 (IL-2) high dose - Alone or with cells
Melanoma and renal cell carcinoma
Activates NK and CTL
Toxic - fever, edema, shock
2. Tumor necrosis factor (TNF-a) - Carcinoma
Activates NK activity
Hairy B cell leukemia, renal cell carcinoma, melanoma, Kaposi sarcoma, hematologic cancers
4. IFN-g : Increases Cl II MHC expression. Ovarian carcinoma
5. Hematopoietic growth factors: Overcome neutropenia
Granulocyte-macrophage colony stimulating factor (GM-CSF)
Introduce cytokine genes for IL-2, IL-4, IL-12, IFN-g orGM-CSF into tumor cells.
By Male, Brostoff, Roth and Roitt