Do innate killing mechanisms activated by inflammasomes have a role in treating melanoma?

Abdullah Al Emran; Hsin-Yi Tseng; Mikaela C Coleman; Jessamy Tiffen; Stuart Cook; Helen M McGuire; Stuart Gallagher; Carl Feng; Peter Hersey

doi:10.1111/pcmr.12870

Do innate killing mechanisms activated by inflammasomes have a role in treating melanoma?

Pigment Cell Melanoma Res. 2020 Sep;33(5):660-670. doi: 10.1111/pcmr.12870. Epub 2020 Feb 20.

Authors

Abdullah Al Emran^{1

2}, Hsin-Yi Tseng^{1

2}, Mikaela C Coleman^{3

4}, Jessamy Tiffen^{1

2}, Stuart Cook^{1

2}, Helen M McGuire^{5

6

7}, Stuart Gallagher^{1

2}, Carl Feng^{3

4}, Peter Hersey^{1

2}

Affiliations

¹ Melanoma Immunology and Oncology Group, The Centenary Institute, Royal Prince Alfred Hospital, University of Sydney, Camperdown, New South Wales, Australia.
² Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
³ Immunology and Host Defence Group, Department of Infectious Diseases and Immunology, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
⁴ Tuberculosis Research Program, Centenary Institute, Camperdown, New South Wales, Australia.
⁵ Ramaciotti Facility for Human Systems Biology, The University of Sydney, Sydney, New South Wales, Australia.
⁶ Discipline of Pathology, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
⁷ Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.

Abstract

Melanoma, as for many other cancers, undergoes a selection process during progression that limits many innate and adaptive tumor control mechanisms. Immunotherapy with immune checkpoint blockade overcomes one of the escape mechanisms but if the tumor is not eliminated other escape mechanisms evolve that require new approaches for tumor control. Some of the innate mechanisms that have evolved against infections with microorganisms and viruses are proving to be active against cancer cells but require better understanding of how they are activated and what inhibitory mechanisms may need to be targeted. This is particularly so for inflammasomes which have evolved against many different organisms and which recruit a number of cytotoxic mechanisms that remain poorly understood. Equally important is understanding of where these mechanisms will fit into existing treatment strategies and whether existing strategies already involve the innate killing mechanisms.

Keywords: IL-1β; TCGA; adaptive resistance; inflammasomes; innate killing; melanoma; pyroptosis.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Cytotoxicity, Immunologic*
Drug Repositioning
Ferroptosis
Humans
Immunity, Innate*
Inflammasomes / metabolism*
Melanoma / immunology*
Melanoma / pathology*

Substances

Inflammasomes