15 imunologi tumor

8/19/2019 15 Imunologi Tumor

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Tumor Immunology

Wirsma Arif Harahap

Surgical Oncologist

Surgery Department

Andalas Medical School


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Immune System

A complex of

lymphoid organs• highly specializedcells

• circulatory systemseparate fromblood essels


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Immune System

• !ymphatic esselsform a circulatorysystem that operatesin close partnership

"ith blood circulation• #arries lymph$ a %uid

that contains Ws'chie%y lymphocytes(

• !ymph nodes proide)meeting grounds*


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+our ,rimary +unctions

• -ecognition of self

– self.tolerance

– immunological

priilege• Immunosureillance

• Intracellularhormones

• Defense againstinfection


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&acteria

Tubercule bacillusStaphylococci

+ungi

Candida albicans

/irus

In%uenza

Polio mellitus

,arasites

Tape"orms

Malaria

Helminths

-ole of the immunesystem is to protect

from0


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1osinophil

Monocyte

Macrophage

2eutrophil

&asophil

Origin of cells inoledin the immune response

Haemopoietic stem cell

& cell Thymus23 cell

Dendritic cell

Mast cell

,lasmacell

#D4 T cell

Myeloid progenitor

!ymphocyteprogenitor

#D5 T cell


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6 Types of Actions of the Immune System

78 Mechanical

98 2on.speci:c 'innateimmunity(

68 Speci:c ' adaptie immunity (


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Overview of immune responses


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Interactions between innate and& adaptive immunity

78 Innate immunity ;< Ag presentation 'by Dendritic cells(

98 Adaptie immunity ;< Ag recognition 'by T = &lymphocytes(


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Evidence for the role of immunesystem in tumor rejection

Spontaneous regressionInltration of tumors by

lymphocytes and macrophages

Regression of metastases afterremoval of primary tumorRegression after chemotherapyLymphocyte proliferation in

draining lymph nodesHigher incidence of cancer after

immunosuppression/immunodeci

ency (I!S" neonates" aged"


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Association bet"eenimmunode:ciency and

cancer

Association bet"eenimmunode:ciency and

cancer

primary'inherited(immunode:ciency

lymphomas

&ur>itt?s lymphoma malaria

secondary'ac@uired(immunode:ciency

lymphoma$ cericalcancer$ lier cancer$s>in cancer$ 3aposi?ssarcoma8

autoimmunity

lymphoma

malignancy

cause ofimmuno.de:ciency


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Tumors stimulate an immuneresponse

Tumors stimulate an immuneresponse

Animals can be immunized againsttumors

Immunity is transferable fromimmune to nae animals

Tumor speci:c antibodies and cell

hae been detected in humans"ith some malignancies

Animals can be immunized againsttumors

Immunity is transferable fromimmune to nae animals

Tumor speci:c antibodies and cell

hae been detected in humans"ith some malignancies


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1tiology Of Tumor7( Inherited 0 1xpression of inherited oncogene

e8g8 iral gene incorporated into host gene

9( /iral0 . Human papilloma$ herpes type 9$ H&/$ 1&/ 'D2A( . Human T.cell leuc>emia irus '-2A(

6( #hemical0 . ,oly cyclic hydrocarbons cause sarcomas . Aromatic amines cause mammary carcinoma

. Al>yl nitroso amines cause hepatoma

4( -adiological0 Bltraiolet = ionizing irradiation

C( Spontaneous0 failure in the cellular gro"th control


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Tumor Associated Antigens

( /iral Antigen 0

a. /iral proteins and glycoproteins b. 2e" antigens produced by irally infected host

cells under control of iral nucleic acid

9( Tumor speci:c antigens 0 . Tumor cells deelop ne" antigen speci:c to

their carcinogens

6( Tumor speci:c transplantation antigens 0

. Tumor cells express ne" MH# antigens due to

alteration of normally present MH# antigens


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Tumor Associated Antigens

4( Oncofetal antigens0

a. #arcino.embryonic antigens '#1A(

. 2ormally expressed during fetal life on fetal gut

. -eappearance in adult life0

EIT$ pancreas$ biliary system and cancer breast

b. Alpha fetoprotein0

. 2ormally expressed in fetal life

. -eappearance in adult lifeF hepatoma


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Immunity against

tumor

Immunity against

tumorAll components$ speci:c and

nonspeci:c$ humoral andcellular aGect tumor progressionand gro"th

All components$ speci:c and

nonspeci:c$ humoral andcellular aGect tumor progressionand gro"th

ti d


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ntigens e$pressed ontumor cells

%ajor Histocompatabil&omple$ antigens

'S'

''

'S' uni)ue to a tumor*lay an important role in tumor rejection+

'' shared by normal and tumor cells'umor,associated developmental g ('!#

'umor,associated viral g ('-#

Tumor.speci:ctransplantation Ag

Tumor.associatedtransplantation Ag


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Tumor associated transplantation

antigens0 shared Ag on irally induced tumors

Tumor associated transplantation

antigens0 shared Ag on irally induced tumors


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Discovery of tumor specific

transplantation antigens, TSTA


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'umor,ssociated !evelopmental gs

.ound on cancer cells and onfetal cells+

!o not trigger anti,tumorimmunity+

sed in diagnosis+

lpha,fetoprotein(.*#&ancers of liver

&arcinoembryonic g (&E#

colorectal cancer ,


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1scape fromimmunosureillance


Lack ofNeo-antigens


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!ac> of2eo.antigens


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!ac> ofclass I MH#


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Tumors secreteImmunosuppressiemolecules


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Tumors shed theirneo.antigens


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'umors escape the action of &'L by not e$pressing 05 6hichprovides 7nd signal involved in ' cell activation

tumor

&'L

tumorg

&lass I %H&

05&!78

umors may fail to e$press costimulator

olecules involved in ' cell activation+


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Btility of Immunology

in#ancer Treatment


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se of tumor associatedantigens

-aise monoclonal antibodiesBse antibodies for diagnosis

Bse antibodies for therapy

Stimulate the in vivo speci:c

responseSpeci:c actie treatmentSpeci:c passie treatmentAduant therapy to augment

speci:c immunity


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Bse of tumor associated antigensmonoclonal antibodies

Bse of tumor associated antigensmonoclonal antibodies


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Monoclonal antibodies0use as a diagnostic toolMonoclonal antibodies0use as a diagnostic tool


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Immunotherapy of tumorsImmunotherapy of tumors

non.speci:c

E$ ,ropionibacterium acne$leamisole$ etc8

>illed tumor cells$ puri:ed orrecombinant Ag

speci:c

actie immunotherapy

!A3 cells$cyto>ines

non.speci:c

antibodies alone or conugated"ith other agent$ actiated Tcells

speci:

c

passie immunotherapy


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2on.speci:c immunotherapy2on.speci:c immunotherapy

actiate macrophagesand 23 cells

I+2. $ I+2. $ I+2. $ I!.9$ T2+.

cyto>ines

interferon productionpyran$ poly I0#

syntheticmolecules

actiate macrophagesand 23 cells 'ia

cyto>ines(

E$ P. acnes$muramyl

dipeptide

bacterialproducts


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increased expressionof class.I MH#$possible anti tumoreGect

remission of hairycell leu>emia$"ea> eGect oncarcinomas

I+2

I+2 increased expressionof class.I MH#$ Tcand 23 cellactiation

remission ofoarian carcinoma

I!.9 T cell proliferationand actiation$ 23cell actiation

remission in renalcell carcinoma and

melanoma

T2+ macrophage andlymphocyteactiation

reduction inmalignant ascites

#yto>ine immunotherapy#yto>ine immunotherapy


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ctive Immuni9ation 'he host

actively elicits an immuneresponse+

Specic

-accination 6ith viral gs e+g+Hepatitis 0 virusHuman *apilloma virus (H*-#


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Than> ou

15 imunologi tumor

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