Tumor

Tumor Immunology
Immunology

 evidence
evidence forfor immune
immune reactivity
reactivity against
against
tumor
tumor

 changes
changes in in cellular
cellular characteristics
characteristics due
due
to
to malignancy
malignancy

 tumor
tumor and
and host
host components
components which
which
affect
affect tumor
tumor progression
progression

 use
use of
of tumor
tumor antigens
antigens in
in diagnosis
diagnosis and
and
immunotherapy
immunotherapy
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Evidence
Evidence for
for immunosurveillance
immunosurveillance
Infiltration of malignant tissue

2
 Association
Association between
between
immunodeficiency
immunodeficiency and
and cancer
cancer
cause of immuno- malignancy
deficiency
 primary (inherited) lymphomas
immunodeficiency
 secondary (acquired) lymphoma, cervical cancer,
immunodeficiency liver cancer, skin cancer,
Kaposi’s sarcoma.
 malaria Burkitt’s lymphoma

 autoimmunity lymphoma

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 Tumors
Tumors stimulate
stimulate an
an immune
immune
response
response

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

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 Neo-antigens
Neo-antigens of
of immunologic
immunologic
significance
significance on
on tumor
tumor cells
cells

 Oncofetal/differentiation
 Oncofetal/differentiation antigens
antigens
 Alpha-feto-protein (AFP)
Alpha-feto-protein (AFP)
 Cracino embryonic antigen (CEA)
Cracino embryonic antigen (CEA)
 CALLA (common acute lymphoblastic leukemia antigen)
CALLA (common acute lymphoblastic leukemia antigen)

 Tumor-associated
 Tumor-associated transplantation
transplantation antigens
antigens
 Tumor specific transplantation antigen
Tumor specific transplantation antigen
 Virus associated shared antigens
Virus associated shared antigens

5
 Alpha
Alpha fetoprotein:
fetoprotein: clinical
clinical
use
use

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

6
Alpha
Alpha fetoprotein:
fetoprotein: clinical
clinical use
use

7
Alpha
Alpha fetoprotein:
fetoprotein: concentrations
concentrations

 Normal
 Normal concentration:
concentration: <20
<20 ng/ml
ng/ml
 Abnormal
 Abnormal concentrations
concentrations
100-350
 100-350 possible
possible hepatoma
hepatoma
350-500
 350-500 probable
probable hepatoma
hepatoma
500-100
 500-100 likely
likely hepatoma
hepatoma
>1000
 >1000 HEPATOMA
HEPATOMA

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Carcinoembryonic
Carcinoembryonic antigen:
antigen:
clinical
clinical use
use

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

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Carcinoembryonic
Carcinoembryonic antigen:
antigen:
clinical
clinical use
use

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Carcinoembryonic
Carcinoembryonic antigen:
antigen:
clinical
clinical use
use

CEA
CEA as
as aa diagnostic
diagnostic adjunct
adjunct


 Symptomatic
Symptomatic patient
patient
 Elevated
 Elevated value
value 5-10
5-10 times
times the
the
upper
upper limit
limit
Normal
Normal value
value <10ng/ml
<10ng/ml

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Tumor
Tumor associated
associated transplantation
transplantation
antigens:: shared
antigens sharedAg
Agon
onvirally
virallyinduced
inducedtumors
tumors

12
 Tumor
Tumor associated
associated transplantation
transplantation
antigens:: unique
antigens uniqueAg
Agon
onchemically
chemicallyinduced
inducedtumors
tumors

13
Immunity
Immunity against
against tumor
tumor

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

14
Escape
Escape from
from immunosurveillance
immunosurveillance

Lack of
Neo-antigens

15
Escape
Escape from
from immunosurveillance
immunosurveillance

Lack of
co-stimulatory
molecules

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Escape
Escape from
from immunosurveillance
immunosurveillance

Lack of
class I MHC

17
 Escape
Escape from
from immunosurveillance
immunosurveillance

Tumors secrete
Immunosuppressive
molecules

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Escape
Escape from
from immunosurveillance
immunosurveillance

Tumors shed their

neo-antigens

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Use
Use of
of tumor
tumor associated
associated antigens
antigens

Raise
 Raise monoclonal
monoclonal antibodies
antibodies
 Use antibodies for diagnosis
Use antibodies for diagnosis
 Use
Useantibodies
antibodiesfor
for therapy
therapy

Stimulate
 Stimulate the
the in
in vivo
vivo specific
specific response
response
 Specific active treatment
Specific active treatment
 Specific
Specificpassive
passivetreatment
treatment
 Adjuvant therapy to augment specific
Adjuvant therapy to augment specific
immunity
immunity

20
Use
Use of
of tumor
tumor associated
associated antigens
antigens
monoclonal
monoclonal antibodies
antibodies

21
Monoclonal
Monoclonal antibodies:
antibodies:
use
use as
as aa diagnostic
diagnostic tool
tool

22
 Immunotherapy
Immunotherapy of
of tumors
tumors
active immunotherapy
specific killed tumor cells, purified or
recombinant Ag
non- specific
BCG, Propionibacterium acne,
levamisole, etc.

passive immunotherapy
non-specific LAK cells, cytokines
antibodies alone or conjugated with
specific
other agent, activated T cells

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 Non-specific
Non-specific immunotherapy
immunotherapy
bacterial products
BCG, P. acnes, activate macrophages and
muramyl dipeptide NK cells (via cytokines)

synthetic molecules
pyran, poly I:C interferon production

cytokines
IFN-, IFN-, IFN-, activate macrophages
IL-2, TNF- and NK cells
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 Cytokine
Cytokine immunotherapy
immunotherapy

remission of hairy cell increased expression of

IFN-, - leukemia, weak effect class-I MHC, possible
on carcinomas anti tumor effect

remission of ovarian increased expression of

IFN- carcinoma class-I MHC, Tc and
NK cell activation

remission in renal cell T cell proliferation and

IL-2 carcinoma and activation, NK cell
melanoma activation

reduction in malignant macrophage and

TNF- ascites lymphocyte activation

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Genetic
Genetic approaches
approaches to
to
cancer
cancer treatment
treatment

 Transfection
 Transfection with
with genes
genes
Cytokines
 Cytokines
Class
 Class II MHC
MHC
Co-stimulatory
 Co-stimulatory molecules
molecules

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