Cancer and the immune system What is cancer? What is the immune response to cancer? Prospects for immune therapies
Cancer cells are out of control! Usually derived from a single cell, forming a tumor Benign tumors are noninvasive; malignant tumors can invade and spread Cancers are classified according to their origin Blood cell cancers: leukemias and lymphomas
How do cells become “transformed” into malignant cells? Radiation Carcinogens Viruses expression of oncogenes (aberrant versions of proto-oncogenes
Types of regulatory genes Proto-oncogenes- induce proliferation (in various ways) Tumor suppressors- inhibit cell proliferation Regulators of apoptosis Defects in any of these can lead to uncontrolled cell growth
Immune system tumors Solid or systemic? Acute or chronic? Immature or mature cells? Myelogenous or lymphocytic?
Tumor-specific antigens found only on tumors Tumor-associated antigens- may be gene products that normally are not expressed (or at abnormal levels) Can these be isolated and used as vaccines? Diagnosis? Therapy?
Most tumor antigens are NOT unique to tumors Often these are fetal proteins (growth factor receptors, e.g.) CEA- carcinoembryonic antigen AFP- alpha-fetoprotein
Immune response to tumors (after all, it’s altered self) Probably cell-mediated response Many tumors reduce MHC Class I expression NK cells can kill these Also macrophages add NK cells can attack antibody-coated tumor cells (ADCC) Immune surveillance?
im Tumors can evade immune response Antitumor antibody can block T cell responses Tumors can modulate antigens Tumors can reduce MHC Class I expression Tumors can reduce “second signal” expression
Strategies for immunotherapy Make cells more immunogenic better CTL activation “ vaccine” cells?
Cytokine therapy Many have been tried: (thanks to recombinant DNA technology Problems: complexity of cytokine interactions hard to administer serious side effects
LAK cells (lymphokine-activated killers) grow blood cells in high levels of IL-2 produce mostly NK cells (NOT tumor- specific) TILs tumor-infiltrating lymphocytes may have more tumor-specific activity and need less IL-2
Cancer vaccines? Antigenic peptides (tumor-specific and immunogenic Delivery (recombinant vaccines) Will they be effectively presented to T cells? Some viral vaccines (e.g., against HPV) may be helpful There is much to be done.