innate immunity and inflammation...• innate immunity: immunity that is naturally present and is...
TRANSCRIPT
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ISBTc ISBTc ‐‐
Primer on Tumor Immunology and Biological Therapy of CancerPrimer on Tumor Immunology and Biological Therapy of Cancer
Innate Immunity and Innate Immunity and InflammationInflammation
Willem Overwijk, Ph.D.Willem Overwijk, Ph.D.
MD Anderson Cancer CenterMD Anderson Cancer Center
Center for Cancer Immunology ResearchCenter for Cancer Immunology Research
Houston, TXHouston, TX
www.allthingsbeautiful.com
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Innate Immunity and InflammationInnate Immunity and Inflammation
• Definitions• Cells and Molecules
• Innate Immunity and Inflammation in Cancer
• Bad Inflammation
• Good Inflammation
• Therapeutic Implications
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Innate Immunity and InflammationInnate Immunity and Inflammation
• Definitions• Cells and Molecules
• Innate Immunity and Inflammation in Cancer
• Bad Inflammation
• Good Inflammation
• Therapeutic Implications
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• Innate Immunity: Immunity that is naturally present
and is not due to prior sensitization to an antigen; generally
nonspecific. It is in contrast to acquired/adaptive immunity.
Adapted from Merriam‐Webster Medical Dictionary
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• Innate Immunity: Immunity that is naturally present
and is not due to prior sensitization to an antigen; generally
nonspecific. It is in contrast to acquired/adaptive immunity.
• Inflammation:
a local response to tissue injury
– Rubor (redness)
– Calor (heat)
– Dolor (pain)
– Tumor (swelling)
Adapted from Merriam‐Webster Medical Dictionary
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““Innate ImmunityInnate Immunity””
and and ““InflammationInflammation””
are vague terms are vague terms
•• Specific cell types and molecules Specific cell types and molecules orchestrate specific types of inflammationorchestrate specific types of inflammation
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““Innate ImmunityInnate Immunity””
and and ““InflammationInflammation””
are vague terms are vague terms
•• Specific cell types and molecules Specific cell types and molecules orchestrate specific types of inflammationorchestrate specific types of inflammation
•• Innate Immunity A Innate Immunity A ≠≠
Innate Immunity BInnate Immunity B
•• Inflammation A Inflammation A ≠≠
Inflammation BInflammation B
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CD4CD4++
T cellT cell
Zhou et al., Immunity, 2009
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CD4CD4++
T cell: Th1 or Th2?T cell: Th1 or Th2?
Zhou et al., Immunity, 2009
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CD4CD4++
T cell: Th1 or Th2?T cell: Th1 or Th2?
Zhou et al., Immunity, 2009
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CD4CD4++
T cell: Th1 or Th2 or Th17 or T cell: Th1 or Th2 or Th17 or Th9 or Treg or Tfh or ?Th9 or Treg or Tfh or ?
Zhou et al., Immunity, 2009
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Today, the term Today, the term ““CD4CD4++
T cellT cell””
can can mean many thingsmean many things
Zhou et al., Immunity, 2009
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““Innate ImmunityInnate Immunity””
and and ““InflammationInflammation”” can mean many thingscan mean many things
•• Specific cell types and molecules Specific cell types and molecules orchestrate specific types of inflammationorchestrate specific types of inflammation
•• Innate Immunity A Innate Immunity A ≠≠
Innate Immunity BInnate Immunity B
•• Inflammation A Inflammation A ≠≠
Inflammation BInflammation B
•• Some immune responses Some immune responses promotepromote cancer, others cancer, others suppresssuppress
itit
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Innate Immunity and InflammationInnate Immunity and Inflammation
Functions:
• Rapid response to tissue damage
• Limit spread of infection
• Initiate adaptive immune response (T, B)
• Initiate tissue repair
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Innate Immunity and Inflammation:Innate Immunity and Inflammation: A Paper CutA Paper Cut
Janeway, Immunobiology, 7th
Ed.
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Innate Immunity and Inflammation:Innate Immunity and Inflammation: A Paper CutA Paper Cut
Janeway, Immunobiology, 7th
Ed.
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Innate Immunity and Inflammation:Innate Immunity and Inflammation: A Paper CutA Paper Cut
Janeway, Immunobiology, 7th
Ed.
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Innate Immunity and Inflammation:Innate Immunity and Inflammation: A Paper CutA Paper Cut
Janeway, Immunobiology, 7th
Ed.
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Innate Immunity and InflammationInnate Immunity and Inflammation
• Definitions• Cells and Molecules
• Innate Immunity and Inflammation in Cancer
• Bad Inflammation
• Good Inflammation
• Therapeutic Implications
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Innate Immune Molecules:Innate Immune Molecules: CyclooxygenaseCyclooxygenase‐‐2 (COX2 (COX‐‐2)2)
Recognize• inflammation
Cause• inflammation
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Innate Immune Molecules:Innate Immune Molecules: Complement SystemComplement System
Recognize• pathogens• antibodies• lectins
Cause• pathogen clearance• chemotaxis• inflammation
Janeway, Immunobiology, 7th
Ed.
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Innate Immune Molecules:Innate Immune Molecules: type I IFN(type I IFN(‐‐))
• Induced by infection/danger• Antiviral/Antiproliferative• Increase innate and adaptive immunity
• Cause inflammation
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Innate Immune CellsInnate Immune Cells
Janeway, Immunobiology, 7th
Ed.
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Innate Immune CellsInnate Immune Cells
Janeway, Immunobiology, 7th
Ed.
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Innate Immune CellsInnate Immune Cells
Janeway, Immunobiology, 7th
Ed.
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Innate Immune Cells: granulocytesInnate Immune Cells: granulocytes
( )
AntigenPresentation
Recognize• pathogens• antibodies
Cause• pathogen clearance• inflammation
Janeway, Immunobiology, 7th
Ed.
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Innate Immune Cells: phagocytesInnate Immune Cells: phagocytes
MonocyteBlood precursor of tissue Macrophages andDendritic Cells
Recognize• pathogens• antibodies
Cause• pathogen clearance• adaptive immunity• inflammation
Janeway, Immunobiology, 7th
Ed.
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Innate Immune Cells:Innate Immune Cells: NK, NKT and NK, NKT and
T cellsT cells
Recognize• pathogens• stressed cells• “altered self”
Cause• pathogen clearance• stressed/abnormal cell clearance• inflammation
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Danger signals start inflammationDanger signals start inflammation
PATHOGENS DAMAGE
Rubartelli & Lotze, Trends in Immunology 2007
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Danger signals start inflammationDanger signals start inflammation
PATHOGENS DAMAGE
Rubartelli & Lotze, Trends in Immunology 2007
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Receptors sense Danger: PathogensReceptors sense Danger: Pathogens
Kawai & Akira, Nat. Immunol. 2010
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Receptors sense Danger: DamageReceptors sense Danger: Damage
Kawai & Akira, Nat. Immunol. 2010
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Innate Immunity and InflammationInnate Immunity and Inflammation
• Definitions• Cells and Molecules
• Innate Immunity and Inflammation in Cancer
• Bad Inflammation
• Good Inflammation
• Therapeutic Implications
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Innate Immunity and InflammationInnate Immunity and Inflammation in Cancerin Cancer
• Outcomes vary:
‐
Promote cancer (Bad
inflammation)
‐
Suppress cancer (Good
inflammation)
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Innate Immunity and InflammationInnate Immunity and Inflammation
• Definitions• Cells and Molecules
• Innate Immunity and Inflammation in Cancer
• Bad Inflammation
• Good Inflammation
• Therapeutic Implications
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DANGERcellular damage caused by• pathogens• physical damage• chemicals• UV• etc
Bad Inflammation Causes CancerBad Inflammation Causes Cancer
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IMMUNE RESPONSEINFLAMMATIONDANGER
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DANGERIMMUNE RESPONSEINFLAMMATION
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IMMUNE RESPONSEINFLAMMATION
COLLATERAL DAMAGE
DANGER
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IMMUNE RESPONSEINFLAMMATION
COLLATERAL DAMAGE
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IMMUNE RESPONSEINFLAMMATIONDANGER
COLLATERAL DAMAGE
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IMMUNE RESPONSEINFLAMMATION
CHRONICDANGER
COLLATERAL DAMAGE
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IMMUNE RESPONSEINFLAMMATION
CHRONICDANGER
COLLATERAL DAMAGE
CHRONIC
CHRONIC
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IMMUNE RESPONSEINFLAMMATION
CHRONICDANGER
COLLATERAL DAMAGE
CHRONIC
CHRONIC
CANCER
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IMMUNE RESPONSEINFLAMMATION
COLLATERAL DAMAGE
CANCER
CHRONICCHRONIC
CHRONIC
DANGER
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IMMUNE RESPONSEINFLAMMATION
COLLATERAL DAMAGE
CANCER
CHRONICCHRONIC
CHRONIC
DANGER
cancer: a “never‐healing wound”
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Inflammation can Promote Cancer:Inflammation can Promote Cancer: collaboration with Kcollaboration with K‐‐ras mutationras mutation
Takahashi et al. , Cancer Cell
2010
4 cigarettes per day
nosmoking
KK‐‐ras mutationras mutation&&
normalnormal
myeloid cellsmyeloid cells
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Inflammation can Promote Cancer:Inflammation can Promote Cancer: collaboration with Kcollaboration with K‐‐ras mutationras mutation
Takahashi et al. , Cancer Cell
2010
4 cigarettes per day
nosmoking
KK‐‐ras mutationras mutation&&
normalnormal
myeloid cellsmyeloid cells
KK‐‐ras mutationras mutation++
IKKIKK‐‐//‐‐
myeloid cellsmyeloid cells
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Inflammation can Promote Cancer:Inflammation can Promote Cancer: collaboration with Kcollaboration with K‐‐ras mutationras mutation
Takahashi et al. , Cancer Cell
2010
4 cigarettes per day
nosmoking
KK‐‐ras mutationras mutation&&
normalnormal
myeloid cellsmyeloid cells
KK‐‐ras mutationras mutation++
IKKIKK‐‐//‐‐
myeloid cellsmyeloid cells
• ↓ NF‐B• ↓ pSTAT3• ↓ IL‐6• ↓ neutrophils• ↓ angiogenesis
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Inflammation can Promote Cancer:Inflammation can Promote Cancer: collaboration with HPV E6/E7 oncogenecollaboration with HPV E6/E7 oncogene
De Visser et al., Cancer Cell
2005Andreu et al., Cancer Cell
2010
TUMOR
tumor‐inducedANTIBODIES
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Meira et al., J. Clin. Invest.
2008
Inflammation can Cause MutationInflammation can Cause Mutation
days post acutedays post acutegut inflammationgut inflammation
Able to repair DNAAble to repair DNA
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Meira et al., J. Clin. Invest.
2008
Inflammation can Cause MutationInflammation can Cause Mutation
days post acutedays post acutegut inflammationgut inflammation
Able to repair DNAAble to repair DNA
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Meira et al., J. Clin. Invest.
2008
Inflammation can Cause MutationInflammation can Cause Mutation
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Meira et al., J. Clin. Invest.
2008
Inflammation can Cause MutationInflammation can Cause Mutation
deoxyguanosine 8‐hydroxydeoxyguanosine
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Tumors can induce bad inflammationTumors can induce bad inflammation
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Bronte et al., J. Immunol. 1999
Tumors can induce bad inflammationTumors can induce bad inflammationSpleen (no tumor)
Spleen (subcut. tumor)
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Marigo et al., Immunity
2010
Tumors can induce bad inflammationTumors can induce bad inflammation
NormalNormalimmune systemimmune system
++T cell treatmentT cell treatment
Tumors induceTumors inducebad inflammationbad inflammation Blocks treatmentBlocks treatment
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Marigo et al., Immunity
2010
Tumors can induce bad inflammationTumors can induce bad inflammation
NormalNormalimmune systemimmune system
++T cell treatmentT cell treatment
CebpbCebpb‐‐deficientdeficientimmune systemimmune system
++T cell treatmentT cell treatment
Tumors induceTumors inducebad inflammationbad inflammation Blocks treatmentBlocks treatment
Tumors cannot induceTumors cannot inducebad inflammationbad inflammation Treatment worksTreatment works
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Ugel et al., Curr. Opin. Pharmacol.
2010
Tumors can induce bad inflammationTumors can induce bad inflammation
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Tumors can induce bad inflammationTumors can induce bad inflammation Oncogenic STAT3Oncogenic STAT3
Yu et al., Nat. Rev. Cancer
2009
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Tumors can induce bad inflammationTumors can induce bad inflammation Oncogenic STAT3Oncogenic STAT3
Yu et al., Nat. Rev. Cancer
2009
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Sumimoto et al., J. Exp. Med..
2006
Mutations can Drive Bad InflammationMutations can Drive Bad Inflammation
controlshRNA
BRAFshRNA
controlshRNA
BRAFshRNA
controlshRNA
BRAFshRNA
Mutated BRAF Mutated BRAF tumor tumor
cells producecells producebad, ibad, imunosuppressive munosuppressive
cytokinescytokines
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Sumimoto et al., J. Exp. Med..
2006
Mutations can Drive Bad InflammationMutations can Drive Bad Inflammation
controlshRNA
BRAFshRNA
controlshRNA
BRAFshRNA
controlshRNA
BRAFshRNA
Mutated BRAF Mutated BRAF tumor tumor
cells producecells producebad, ibad, imunosuppressive munosuppressive
cytokinescytokines
block production of good block production of good
cytokines in DCscytokines in DCs
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Conclusion: Inflammation and CancerConclusion: Inflammation and Cancer
• Inflammation can Cause Cancer
• Inflammation can Cause Mutation
• Mutation can Cause Inflammation
• Mutation can Cause Cancer
• Cancer can Cause Inflammation
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Inflammation and Cancer:Inflammation and Cancer: A Vicious CycleA Vicious Cycle
CANCER
INFLAMMATION
MUTATION
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Mantovani et al., Nature
2009Hanahan & Weinberg, Cell
2000
Classic Hallmarks of CancerClassic Hallmarks of Cancer
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Mantovani et al., Nature
2009Hanahan & Weinberg, Cell
2000
Inflammation is (now) a Classic Inflammation is (now) a Classic Hallmark of CancerHallmark of Cancer
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Mantovani et al., Nature
2009Hanahan & Weinberg, Cell
2000
Inflammation is (now) a Classic Inflammation is (now) a Classic Hallmark of CancerHallmark of Cancer
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Innate Immunity and InflammationInnate Immunity and Inflammation
• Definitions• Cells and Molecules
• Innate Immunity and Inflammation in Cancer
• Bad Inflammation
• Good Inflammation
• Therapeutic Implications
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Good Good vs.vs.
Bad InflammationBad Inflammation in Cancerin Cancer
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IFNIFN‐‐
Suppresses Human Tumor Suppresses Human Tumor Development Development
Toyoda et al., J. Med. Genetics 2010
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Toyoda et al., J. Med. Genetics 2010
At 17 years of age, the patient developed multifocal Squamous Cell Carcinomas
on the face and both hands. Despite local tumour excision, multiple lesions
occurred and the patient died at 20 years of age of disseminated SCC. Inherited
disorders of IFN-mediated immunity may predispose patients to SCC.
IFNIFN‐‐
Suppresses Human Tumor Suppresses Human Tumor Development Development
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Human Immune System can Suppress Human Immune System can Suppress Existing Tumors for YearsExisting Tumors for Years
1982: patient with primary, resected melanoma
1997: declared disease‐free and “cured”
1998: died of brain hemorrhage, donated kidneys
2000:
‐
kidney recipient 1 died of metastatic donor melanoma
‐
kidney recipient 2 taken off immunosuppression; start IFN‐
‐
kidney recipient 2 rejects kidney and melanoma
MacKie et al., NEJM
2003
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MacKie et al., NEJM
2003
1982: patient with primary, resected melanoma
1997: declared disease‐free and “cured”
1998: died of brain hemorrhage, donated kidneys
2000:
‐
kidney recipient 1 died of metastatic donor melanoma
‐
kidney recipient 2 taken off immunosuppression; start IFN‐
‐
kidney recipient 2 rejects kidney and melanoma
Human Immune System can Suppress Human Immune System can Suppress Existing Tumors for YearsExisting Tumors for Years
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Vajdic & Van Leeuwen , Int. J. Cancer 2009
PostPost‐‐transplant Immunosuppression transplant Immunosuppression Increases Cancer IncidenceIncreases Cancer Incidence
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Type I IFNs Suppress Growth of Type I IFNs Suppress Growth of Transplanted TumorsTransplanted Tumors
IFN‐
receptor
blocking mAb
control mAb
Dunn et al. Nat. Immunol. 2005
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Type I IFNs Suppress Development Type I IFNs Suppress Development of Carcinogenof Carcinogen‐‐Induced TumorsInduced Tumors
MCA carcinogenDunn et al. Nat. Immunol. 2005
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IFNIFN‐‐
treatment enhances antitreatment enhances anti‐‐ cancer vaccinationcancer vaccination
Sikora et al. J. Immunol. 2009
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IFNIFN‐‐
treatment enhances antitreatment enhances anti‐‐ cancer vaccinationcancer vaccination
Sikora et al. J. Immunol. 2009
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Lou et al. , unpublished results
Intratumoral PBS Intratumoral CpG Intravenous CpG
CpG Causes Tumor Inflammation and CpG Causes Tumor Inflammation and Intratumoral T cell AccumulationIntratumoral T cell Accumulation
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CpG Causes Tumor Inflammation and CpG Causes Tumor Inflammation and Intratumoral T cell AccumulationIntratumoral T cell Accumulation
Lou et al. , unpublished results
Tumor size (m
m2 )
Days after Vaccination
P<0.01
0
150
300
450
0 5 10 15
i.t PBSi.t CpGvaccine + i.t PBS vaccine + i.t CpG
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Adapted from Grivennikov et al. Cell
2010
Tumor‐
inducedInflammation
Chronic
InflammationAutoimmunity
Infection
Dietary &
Environment‐
inducedInflammation
Cancer
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Grivennikov et al. Cell
2010
Bottom Line: Inflammation can be Bottom Line: Inflammation can be Good or Bad: Pro or AntiGood or Bad: Pro or Anti‐‐TumorTumor
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In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Block Bad InflammationBlock Bad Inflammation
![Page 85: Innate Immunity and Inflammation...• Innate Immunity: Immunity that is naturally present and is not due to prior sensitization to an antigen; generally nonspecific. It is in contrast](https://reader031.vdocument.in/reader031/viewer/2022012918/5f0272b07e708231d4044fdd/html5/thumbnails/85.jpg)
In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Block Bad InflammationBlock Bad Inflammation
• COX‐2 inhibitor
Aspirin, Celecoxib (colorectal)
![Page 86: Innate Immunity and Inflammation...• Innate Immunity: Immunity that is naturally present and is not due to prior sensitization to an antigen; generally nonspecific. It is in contrast](https://reader031.vdocument.in/reader031/viewer/2022012918/5f0272b07e708231d4044fdd/html5/thumbnails/86.jpg)
In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Block Bad InflammationBlock Bad Inflammation
• COX‐2 inhibitor
Aspirin, Celecoxib (colorectal)
• VEGF blocker
Bevacizumab, Sorafenib (several)
![Page 87: Innate Immunity and Inflammation...• Innate Immunity: Immunity that is naturally present and is not due to prior sensitization to an antigen; generally nonspecific. It is in contrast](https://reader031.vdocument.in/reader031/viewer/2022012918/5f0272b07e708231d4044fdd/html5/thumbnails/87.jpg)
In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Block Bad InflammationBlock Bad Inflammation
• COX‐2 inhibitor
Aspirin, Celecoxib (colorectal)
• VEGF blocker
Bevacizumab, Sorafenib (several)
• IL‐1
blocker
IL‐1Ra (MM)
![Page 88: Innate Immunity and Inflammation...• Innate Immunity: Immunity that is naturally present and is not due to prior sensitization to an antigen; generally nonspecific. It is in contrast](https://reader031.vdocument.in/reader031/viewer/2022012918/5f0272b07e708231d4044fdd/html5/thumbnails/88.jpg)
In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Block Bad InflammationBlock Bad Inflammation
• COX‐2 inhibitor
Aspirin, Celecoxib (colorectal)
• VEGF blocker
Bevacizumab, Sorafenib (several)
• IL‐1
blocker
IL‐1Ra (MM)
• Cytokine Regulators Lenalidomide (MDS, MM)
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In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Block Bad InflammationBlock Bad Inflammation
• COX‐2 inhibitor
Aspirin, Celecoxib (colorectal)
• VEGF blocker
Bevacizumab, Sorafenib (several)
• IL‐1
blocker
IL‐1Ra (MM)
• Cytokine Regulators Lenalidomide (MDS, MM)
• Kill Helicobacter Pylori
Clarithrom./Amoxicillin
(gastric)
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In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Block Bad InflammationBlock Bad Inflammation
• COX‐2 inhibitor
Aspirin, Celecoxib (colorectal)
• VEGF blocker
Bevacizumab, Sorafenib (several)
• IL‐1
blocker
IL‐1Ra (MM)
• Cytokine Regulators Lenalidomide (MDS, MM)
• Kill Helicobacter Pylori
Clarithrom./Amoxicillin
(gastric)
• Remove suppressors Cycl/Fludar + T cells (melanoma)
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In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Block Bad InflammationBlock Bad Inflammation
• COX‐2 inhibitor
Aspirin, Celecoxib (colorectal)
• VEGF blocker
Bevacizumab, Sorafenib (several)
• IL‐1
blocker
IL‐1Ra (MM)
• Cytokine Regulators Lenalidomide (MDS, MM)
• Kill Helicobacter Pylori
Clarithrom./Amoxicillin
(gastric)
• Remove suppressors Cycl/Fludar + T cells (melanoma)
• Cytotoxic Therapy? Radiation/Chemother. (all
cancers)
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In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Block Bad InflammationBlock Bad Inflammation
• COX‐2 inhibitor
Aspirin, Celecoxib (colorectal)
• VEGF blocker
Bevacizumab, Sorafenib (several)
• IL‐1
blocker
IL‐1Ra (MM)
• Cytokine Regulators Lenalidomide (MDS, MM)
• Kill Helicobacter Pylori
Clarithrom./Amoxicillin
(gastric)
• Remove suppressors Cycl/Fludar + T cells (melanoma)
• Cytotoxic Therapy? Radiation/Chemother. (all
cancers)
• Targeted Therapy? TKI inhibitors (many cancers)
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In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Induce Good InflammationInduce Good Inflammation
![Page 94: Innate Immunity and Inflammation...• Innate Immunity: Immunity that is naturally present and is not due to prior sensitization to an antigen; generally nonspecific. It is in contrast](https://reader031.vdocument.in/reader031/viewer/2022012918/5f0272b07e708231d4044fdd/html5/thumbnails/94.jpg)
In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Induce Good InflammationInduce Good Inflammation
• Bacteria
BCG
(bladder)
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In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Induce Good InflammationInduce Good Inflammation
• Bacteria
BCG
(bladder)
• TLR agonists Imiquimod
(basal cell carcinoma)
CpG
(B cell lymphoma)
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In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Induce Good InflammationInduce Good Inflammation
• Bacteria
BCG
(bladder)
• TLR agonists Imiquimod
(basal cell carcinoma)
CpG
(B cell lymphoma)
• Cytokines
IL‐2
(melanoma, renal)IFN‐
(melanoma, renal, CML)
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In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Induce Good InflammationInduce Good Inflammation
• Bacteria
BCG
(bladder)
• TLR agonists Imiquimod
(basal cell carcinoma)
CpG
(B cell lymphoma)
• Cytokines
IL‐2
(melanoma, renal)IFN‐
(melanoma, renal, CML)
• Antibodies
aCTLA4 mAb (melanoma)
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In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Induce Good InflammationInduce Good Inflammation
• Bacteria
BCG
(bladder)
• TLR agonists Imiquimod
(basal cell carcinoma)
CpG
(B cell lymphoma)
• Cytokines
IL‐2
(melanoma, renal)IFN‐
(melanoma, renal, CML)
• Antibodies
aCTLA4 mAb (melanoma)
• Surgery
Danger/inflammation?
(cervical)
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In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Induce Good InflammationInduce Good Inflammation
• Bacteria
BCG
(bladder)
• TLR agonists Imiquimod
(basal cell carcinoma)
CpG
(B cell lymphoma)
• Cytokines
IL‐2
(melanoma, renal)IFN‐
(melanoma, renal, CML)
• Antibodies
aCTLA4 mAb (melanoma)
• Surgery
Danger/inflammation?
(cervical)
• Hem. Stem Cells
Stem Cell Transpl. (leukemia, lymphoma)
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• Bacteria
BCG
(bladder)
• TLR agonists Imiquimod
(basal cell carcinoma)
CpG
(B cell lymphoma)
• Cytokines
IL‐2
(melanoma, renal)IFN‐
(melanoma, renal, CML)
• Antibodies
aCTLA4 mAb (melanoma)
• Surgery
Danger/inflammation?
(cervical)
• Hem. Stem Cells
Stem Cell Transpl. (leukemia, lymphoma)
• T cells
Adoptive T cell Transfer
(melanoma)
In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Induce Good InflammationInduce Good Inflammation
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In the Clinic: Cancer Therapies that In the Clinic: Cancer Therapies that Induce Good InflammationInduce Good Inflammation
• Bacteria
BCG
(bladder)
• TLR agonists Imiquimod
(basal cell carcinoma)
CpG
(B cell lymphoma)
• Cytokines
IL‐2
(melanoma, renal)IFN‐
(melanoma, renal, CML)
• Antibodies
aCTLA4 mAb (melanoma)
• Surgery
Danger/inflammation?
(cervical)
• Hem. Stem Cells
Stem Cell Transpl. (leukemia, lymphoma)
• T cells
Adoptive T cell Transfer
(melanoma)
• Vaccine
PAP‐loaded DCs (prostate)
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Take Home MessagesTake Home Messages
• Inflammation is a classic hallmark of cancer
• Innate Immunity & Inflammation can promote or suppress cancer
• Manipulating immunity can promote or suppress cancer
• Understanding of inflammatory cells & molecules in cancer is limited but growing, allowing therapeutic intervention
Therapy‐induced
Inflammation
Tumor‐induced
Inflammation
Chronic InflammationAutoimmunity
Infection
Dietary & Environment‐
inducedInflammation
Cancer