Tumor Immunology (I): Cancer Immunosurveillance & Immunoediting Masoud H. Manjili Department of Microbiology & Immunology Goodwin Research Building-286 (804) 828-8779
Dec 22, 2015
Tumor Immunology (I):
Cancer Immunosurveillance
& Immunoediting
Masoud H. ManjiliDepartment of Microbiology &
ImmunologyGoodwin Research Building-286
(804) 828-8779
Learning Objectives
Immune surveillance and immune editing of cancer
Immunotherapy of cancer
Goal of Tumor Immunology
The ultimate goal of tumor immunology is to induce clinically effective anti-tumor immune responses that would discriminate between tumor cells and normal cells in cancer patients
Cancer is the second leading causes of death in the US
Types 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)
Lymphoma, Myeloma: diseases of the lymph nodes and spleen that cause excessive production of lymphocytes (5.4% of cancers)
Leukemia: disease of bone marrow causing excessive production of leukocytes (3.4% of all cancers)
Sarcoma: solid tumors of muscles, bone, and cartilage that arise from the embryological mesoderm (1.9% of all cancers)
Etiology of Cancer
1. Transformation of germline cells: inheritable cancers (<10%, Rb, BRCA1, 2)
2. Transformation of somatic cells: noninheritable cancers (>90%)
Environmental factors:UV (skin cancer), chemicals (lung cancer), pathogens (HPV causes cervical cancer, helicobacter causes stomach cancer)
Genetic Factors
Environmental Factors
Discovery of anti-tumor immune response
Evidence for Tumor Immunity
Spontaneous regression: melanoma, lymphoma
Regression of metastases after removal of primary tumor: pulmonary metastases from renal carcinoma
Infiltration of tumors by lymphocytes and macrophages: melanoma and breast cancer
Lymphocyte proliferation in draining lymph nodes
Higher incidence of cancer after immunosuppression, immunodeficiency (AIDS, neonates), aging, etc.
Anti-tumor immunity via cross priming
Tumor Immunology
Cancer immunosurveilance: immune system can recognize and
destroy nascent transformed cells
Cancer immunoediting: tumors tend to be genetically
unstable; thus immune system can kill and also induce changes in the tumor resulting in tumor escape and recurrence
Evidence for Elimination (cancer
immunosurveillance) Mice lacking perforin show an
increased frequency of lymphomas Mice lacking RAG and STAT1 develop
gut epithelial and breast tumors Mice lacking gamma delta T cells are
susceptible to skin tumors induced by topical application of carciongens
Immunosurveillance is against virus-associated tumors rather than against common spontaneous tumors
Elimination or Tolerance? affinity
Elimination: mutated tumor antigens
Elimination: abnormal expression of antigens
Evidence for Equilibrium (occult tumors)
The occurrence of cancer in recipients of organ transplants: melanoma after kidney transplant
Evidence for Escape (detectable tumors)
1) Immune responses change tumors such that tumors will no longer be seen by the immune system: tumor escape
2) Tumors change the immune responses by promoting immune suppressor cells: immune evasion
Escape: immune system sculpts tumors
GM-CSFVEGFMCP-1
MDSC
Summary Environmental factors such as UV,
chemicals, pathogens (viral and bacterial infections)
Immune responses have a dual function: immunosurveillance and immunoediting of tumor (elimination, equilibrium, escape)
Immunoediting: immune responses can change tumors to be hidden from recognition by the immune system and tumors can promote immune suppressor cells: T regs and myeloid-derived suppressor cells (MDSC)
Suggested Reading
Janeway’s Immunobiology, 7th edition: Chapter 15; Pgs. 672-678