principles of tumour immunology: explaining cellular immunity … · michele teng nov 20th 2019,...
TRANSCRIPT
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Michele TengNov 20th 2019, Singapore
ESMO IO PreceptorshipCancer Immunoregulation and
Immunotherapy Laboratory
QIMR Berghofer MRI
Queensland, Australia
Principles of tumour immunology: Explaining
cellular immunity and immune surveillance
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Disclosures
• I have previously received speaker’s
honorarium and/or travel support from BMS,
MSD, Boehringer Ingelheim, Arcus
Biosciences and Novartis.
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Talk Outline
1. The Cancer Immunity Cycle
- Development of Cellular Immunity to Cancer
2. Immunosurveillance of cancer
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Cells of the immune system
(gd, MAIT)(ILCs)
ILCs –innate lymphoid cells
MAITs –Mucosal associated
invariant T cells
gd T cells – gamma delta T cells
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Hallmarks of Cancer (2017)
Invitrogen
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How does one generate an effective
anti-tumour response?
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The Cancer-Immunity Cycle
Vivier E Nature 2019
Chen and Mellman Immunity 2013 (1)
(2)
(3)
(4)
(5)
(6)
(7)
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The Cancer-Immunity Cycle
Vivier E Nature 2019
Chen and Mellman Immunity 2013
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Not all cell death is equal(at inducing an anti-tumour immune response)
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The Triforce of Immunogenic Cell Death (ICD)
Legrand A et al., Molecular Cell Review 2019
Microbiome
Oncolytic virus
Sting agonist
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The Cancer-Immunity Cycle
Vivier E Nature 2019
Chen and Mellman Immunity 2013
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Priming of tumour-specific T cells by APCs
TCR with the right specificity
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Requirements for effective priming of T cells
Front. Oncol., 10 April 2014 | https://doi.org/10.3389/fonc.2014.00077
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Development of cellular immune response
to tumours
Danger
signals
Memory
TCR
TH1 response
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Tumour-specific and tumour-associated antigens
© QIMR Berghofer Medical Research Institute | 15
(Neoantigens)
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Mutational load correlates with frequency of
tumour neoantigens... & response
Ton N. Schumacher, and Robert D. Schreiber
Science 2015;348:69-74
Estimate of the neoantigen repertoire in human cancer
Synder A et al., NEJM 2014
van Allen et al., Science , 2015, Hugo W et al., Cell 2016MHC
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Smith et al., Nat Rev Cancer 2019
Alternative tumour-specific antigens
Frameshift mutation
hERV - ccRCC
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Galon Nat Rev Drug Discovery 2019
Types of tumour microenvironment
HOT
CD3+
CD8+
COLD
No T cells
ExcludedImmunosuppressed
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Lee and Ruppin JAMA Oncology 2019
Among 36 variables, estimated CD8+ T cell abundance was the most
predictive of response to PD1/PDL1 blockade across cancer types
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The Cancer-Immunity Cycle
Vivier E Nature 2019
Chen and Mellman Immunity 2013
*
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When the Cancer Immunity Cycle is
completed
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The Cancer-Immunity Cycle
Vivier E Nature 2019
Chen and Mellman Immunity 2013
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Immunosurveillance of cancer
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© QIMR Berghofer Medical Research Institute | 24
Smyth et al. JEM 2000, Shankaran et al. Nature 2001Swann et al. J. Clin. Invest. 2007, Koebel et al. Nature 2007Teng et al., JLB 2008; Schreiber..Smyth. Science 2011Teng et al., Cancer Res 2012, Teng et al., JCI 2015
3Es
KILL BATTLE LOSE
Successful
Cancer Immunity
Cycle
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Immunesurveillance occurs during
the process of carcinogenesis
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gene-expression profiling and multispectral imaging on 122 biopsies from 77 pts
Normal Low grade High
grade
SCC
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Main stages of carcinogenesis for lung SCC
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Therapy induced immunoediting
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O’Donnell et al., Nat
Rev Clin Oncol 2019
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68 mel pts
Progressed on Ipi or Ipi-Naïve
Genomics performed before and on
initiation of Nivo
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Should cancer immunotherapy
be given earlier?
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Title of thepresentationSubtitle of the presentation
Basic concepts arguing for the use of neoadjuvant immunotherapy
A/Prof Michele TengQIMR Berghofer Medical Research InstituteBrisbane, Australia
22nd November 2019
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Summary• 7 major steps are required to generate an effective anti-
tumour T cell response
• Cancer immunoediting occurs during the natural progression of tumours but can also occur in patients treated with cancer immunotherapies
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Summary
• Cancer immunoediting exist in humans
• It proceeds through three phases; elimination,
equilibrium and escape
• Cancer immunoediting occurs during the natural
progression of tumours but can also occur in
patients treated with cancer immunotherapies.
• To achieve tumour elimination, it will be essential
to optimally combine therapies to promote
immune activation and T-cell priming, attack
immunosuppressive TME pathways, and sustain
T-cells within tumour tissue.