Tumor Immunology

1
Tumor Immunology

• evidence for immune reactivity against tumor
• changes in cellular characteristics due to
  malignancy
• tumor and host components which affect tumor
  progression
• use of tumor antigens in diagnosis and
  immunotherapy

2
Evidence for immunosurveillance
Infiltration of malignant tissue
3
Association between immunodeficiency and cancer
4
Tumors stimulate an immune response

• Animals can be immunized against tumors
• Immunity is transferable from immune to naïve
  animals
• Tumor specific antibodies and cell have been
  detected in humans with some malignancies

5
Neo-antigens of immunologic significance on tumor
cells

• Oncofetal/differentiation antigens
• Alpha-feto-protein (AFP)
• Cracino embryonic antigen (CEA)
• CALLA (common acute lymphoblastic leukemia
  antigen)
• Tumor-associated transplantation antigens
• Tumor specific transplantation antigen
• Virus associated shared antigens

6
Alpha fetoprotein clinical use

• AFP increases in testicular and liver cancers
• Aids in diagnosis and staging
• Patient management
• Detection of tumors

7
Alpha fetoprotein clinical use
8
Alpha fetoprotein concentrations

• Normal concentration lt20 ng/ml
• Abnormal concentrations
• 100-350 possible hepatoma
• 350-500 probable hepatoma
• 500-100 likely hepatoma
• gt1000 HEPATOMA

9
Carcinoembryonic antigenclinical use

• Adjunct in diagnosis
• Staging and prognosis
• Monitoring response to therapy
• Detection of tumor recurrence

10
Carcinoembryonic antigenclinical use
11
Carcinoembryonic antigenclinical use

• CEA as a diagnostic adjunct
• Symptomatic patient
• Elevated value 5-10 times the upper limit
• Normal value lt10ng/ml

12
Tumor associated transplantation antigens shared
Ag on virally induced tumors
13
Tumor associated transplantation antigens unique
Ag on chemically induced tumors
14
Immunity against tumor

• All components, specific and nonspecific, humoral
  and cellular affect tumor progression and growth

15
Escape from immunosurveillance
Lack of Neo-antigens
16
Escape from immunosurveillance
Lack of co-stimulatory molecules
17
Escape from immunosurveillance
Lack of class I MHC
18
Escape from immunosurveillance
Tumors secrete Immunosuppressive molecules
19
Escape from immunosurveillance
Tumors shed their neo-antigens
20
Use of tumor associated antigens

• Raise monoclonal antibodies
• Use antibodies for diagnosis
• Use antibodies for therapy
• Stimulate the in vivo specific response
• Specific active treatment
• Specific passive treatment
• Adjuvant therapy to augment specific immunity

21
Use of tumor associated antigensmonoclonal
antibodies
22
Monoclonal antibodiesuse as a diagnostic tool
23
Immunotherapy of tumors
active immunotherapy
passive immunotherapy
24
Non-specific immunotherapy
bacterial products
activate macrophages and NK cells (via cytokines)
BCG, P. acnes, muramyl dipeptide
synthetic molecules
interferon production
pyran, poly IC
cytokines
activate macrophages and NK cells
IFN-?, IFN-?, IFN-?, IL-2, TNF-?
25
Cytokine immunotherapy
26
Genetic approaches to cancer treatment

• Transfection with genes
• Cytokines
• Class I MHC
• Co-stimulatory molecules