principles of tumour immunology: explaining cellular immunity … · michele teng nov 20th 2019,...
TRANSCRIPT
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
Disclosures
• I have previously received speaker’s
honorarium and/or travel support from BMS,
MSD, Boehringer Ingelheim, Arcus
Biosciences and Novartis.
Talk Outline
1. The Cancer Immunity Cycle
- Development of Cellular Immunity to Cancer
2. Immunosurveillance of cancer
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
Hallmarks of Cancer (2017)
Invitrogen
How does one generate an effective
anti-tumour response?
The Cancer-Immunity Cycle
Vivier E Nature 2019
Chen and Mellman Immunity 2013 (1)
(2)
(3)
(4)
(5)
(6)
(7)
The Cancer-Immunity Cycle
Vivier E Nature 2019
Chen and Mellman Immunity 2013
Not all cell death is equal(at inducing an anti-tumour immune response)
The Triforce of Immunogenic Cell Death (ICD)
Legrand A et al., Molecular Cell Review 2019
Microbiome
Oncolytic virus
Sting agonist
The Cancer-Immunity Cycle
Vivier E Nature 2019
Chen and Mellman Immunity 2013
Priming of tumour-specific T cells by APCs
TCR with the right specificity
Requirements for effective priming of T cells
Front. Oncol., 10 April 2014 | https://doi.org/10.3389/fonc.2014.00077
Development of cellular immune response
to tumours
Danger
signals
Memory
TCR
TH1 response
Tumour-specific and tumour-associated antigens
© QIMR Berghofer Medical Research Institute | 15
(Neoantigens)
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
Smith et al., Nat Rev Cancer 2019
Alternative tumour-specific antigens
Frameshift mutation
hERV - ccRCC
Galon Nat Rev Drug Discovery 2019
Types of tumour microenvironment
HOT
CD3+
CD8+
COLD
No T cells
ExcludedImmunosuppressed
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
The Cancer-Immunity Cycle
Vivier E Nature 2019
Chen and Mellman Immunity 2013
*
When the Cancer Immunity Cycle is
completed
The Cancer-Immunity Cycle
Vivier E Nature 2019
Chen and Mellman Immunity 2013
Immunosurveillance of cancer
© 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
Immunesurveillance occurs during
the process of carcinogenesis
gene-expression profiling and multispectral imaging on 122 biopsies from 77 pts
Normal Low grade High
grade
SCC
Main stages of carcinogenesis for lung SCC
Therapy induced immunoediting
O’Donnell et al., Nat
Rev Clin Oncol 2019
68 mel pts
Progressed on Ipi or Ipi-Naïve
Genomics performed before and on
initiation of Nivo
Should cancer immunotherapy
be given earlier?
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
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
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.