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

michele.teng@qimrberghofer.edu.au

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

michele.teng@qimrberghofer.edu.au

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.