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Tumor ImmunologyTumor 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

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

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Evidence for immunosurveillanceEvidence for immunosurveillance

Infiltration of malignant tissue

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Association between immunodeficiency and cancer

Association between immunodeficiency and cancer

primary (inherited) immunodeficiency

lymphomas

Burkitt’s lymphoma malaria

secondary (acquired) immunodeficiency

lymphoma, cervical cancer, liver cancer, skin cancer, Kaposi’s sarcoma.

autoimmunity lymphoma

malignancycause of immuno-deficiency

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Tumors stimulate an immune response

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

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

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Neo-antigens of immunologic significance on tumor cells

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

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

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Alpha fetoprotein: clinical use

Alpha fetoprotein: clinical use

AFP increases in testicular and liver cancers

Aids in diagnosis and staging Patient management Detection of tumors

AFP increases in testicular and liver cancers

Aids in diagnosis and staging Patient management Detection of tumors

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Alpha fetoprotein: clinical useAlpha fetoprotein: clinical use

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Alpha fetoprotein: concentrationsAlpha fetoprotein: concentrations

Normal concentration: <20 ng/ml Abnormal concentrations

100-350 possible hepatoma 350-500 probable hepatoma 500-100 likely hepatoma >1000 HEPATOMA

Normal concentration: <20 ng/ml Abnormal concentrations

100-350 possible hepatoma 350-500 probable hepatoma 500-100 likely hepatoma >1000 HEPATOMA

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Carcinoembryonic antigen:clinical use

Carcinoembryonic antigen:clinical use

Adjunct in diagnosis

Staging and prognosis

Monitoring response to therapy Detection of tumor recurrence

Adjunct in diagnosis

Staging and prognosis

Monitoring response to therapy Detection of tumor recurrence

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Carcinoembryonic antigen:clinical use

Carcinoembryonic antigen:clinical use

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CEA as a diagnostic adjunct

Symptomatic patient Elevated value 5-10 times the

upper limit

Normal value <10ng/ml

CEA as a diagnostic adjunct

Symptomatic patient Elevated value 5-10 times the

upper limit

Normal value <10ng/ml

Carcinoembryonic antigen:clinical use

Carcinoembryonic antigen:clinical use

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Tumor associated transplantation antigens: shared Ag on virally induced tumors

Tumor associated transplantation antigens: shared Ag on virally induced tumors

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Tumor associated transplantation antigens: unique Ag on chemically induced tumors

Tumor associated transplantation antigens: unique Ag on chemically induced tumors

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Immunity against tumorImmunity against tumor

All components, specific and nonspecific, humoral and cellular

affect tumor progression and growth

All components, specific and nonspecific, humoral and cellular

affect tumor progression and growth

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Escape from immunosurveillanceEscape from immunosurveillance

Lack of Neo-antigens

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Escape from immunosurveillanceEscape from immunosurveillance

Lack of co-stimulatory

molecules

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Escape from immunosurveillanceEscape from immunosurveillance

Lack of class I MHC

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Escape from immunosurveillanceEscape from immunosurveillance

Tumors secrete

Immunosuppressive

molecules

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Escape from immunosurveillanceEscape from immunosurveillance

Tumors shed their

neo-antigens

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Use of tumor associated antigensUse 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

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

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Use of tumor associated antigensmonoclonal antibodies

Use of tumor associated antigensmonoclonal antibodies

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Monoclonal antibodies:use as a diagnostic toolMonoclonal antibodies:use as a diagnostic tool

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Immunotherapy of tumorsImmunotherapy of tumors

non- specific BCG, Propionibacterium acne, levamisole, etc.

killed tumor cells, purified or recombinant Ag

specific

active immunotherapy

LAK cells, cytokinesnon-specific

antibodies alone or conjugated with other agent, activated T cellsspecific

passive immunotherapy

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Non-specific immunotherapyNon-specific immunotherapy

activate macrophages and NK cells

IFN-, IFN-, IFN-, IL-2, TNF-

cytokines

interferon productionpyran, poly I:C

synthetic molecules

activate macrophages and NK cells (via cytokines)

BCG, P. acnes, muramyl dipeptide

bacterial products

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increased expression of class-I MHC, possible anti tumor effect

remission of hairy cell leukemia, weak effect on carcinomas

IFN-, -

IFN-increased expression of class-I MHC, Tc and NK cell activation

remission of ovarian carcinoma

IL-2T cell proliferation and activation, NK cell activation

remission in renal cell carcinoma and melanoma

TNF-macrophage and lymphocyte activation

reduction in malignant ascites

Cytokine immunotherapyCytokine immunotherapy

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Genetic approaches to cancer treatment

Genetic approaches to cancer treatment

Transfection with genes Cytokines Class I MHC Co-stimulatory molecules

Transfection with genes Cytokines Class I MHC Co-stimulatory molecules