Dr Kendle Maslowski - Microbial and Metabolic Immune Modulation

Introduction

New therapies that target immune responses to kill tumours are an area of rapid growth and hope. While immune checkpoint blockade therapy has led to dramatic improvement for some patients, it still is not applicable for the majority of people affected by cancer. Challenges for immune therapies include poor immune infiltration of tumours, an inhibitory tumour microenvironment as well as immune-related toxicities.

The immune system protects us from infectious agents such as bacteria, viruses and fungi, as well as from malignant growth of our own tissues. Our lab is interested in the intersection between anti-bacterial and anti-tumour responses. Our bodies have both positive (commensals) and negative (pathogenic) interactions with bacteria. On the one hand, microbes that form our gut microbiota are important for instructing and regulating our immune system; While on the other, pathogenic or opportunistic microbes can deviate and manipulate our immune responses to aid their survival and spread, and even be involved in pro-tumourigenic processes.

The concept of bacterial cancer therapy dates to William Coley, who developed ‘Coley’s toxins’, a preparation of heat killed bacteria injected into tumours. Our work largely focuses on the use of live-attenuated Salmonella as a cancer therapy; we are dissecting the mechanisms by which attenuated Salmonella treatment leads to tumour regression, looking at the adaptation of the bacteria to the tumour environment, and the effects on cancer cells and on immune responses. With a detailed mechanistic understanding of bacterial therapy, we aim to achieve optimal engineering of Salmonella to advance towards clinical application.

Lab Report

pdf Maslowski Lab Report (169 KB)

Key Publications

Copland A, Mackie GM, Scarfe L, Lecky DAJ, Gudgeon N, McQuade R, Ono M, Barthel M, Hardt W-D, Ohno H, Dimeloe S, Bending D, Maslowski KM. Salmonella cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity. bioRxiv. 2023;10.1101/2023.01.12.523780:2023.2001.2012.523780.

Mackie GM, Copland A, Takahashi M, Nakanishi Y, Everard I, Kato T, Oda H, Kanaya T, Ohno H, Maslowski KM. Bacterial cancer therapy in autochthonous colorectal cancer affects tumor growth and metabolic landscape. JCI Insight. 2021;6.

Maslowski KM. Metabolism at the centre of the host-microbe relationship. Clin Exp Immunol. 2019;197:193-204.

Allam R, Maillard MH, Tardivel A, Chennupati V, Bega H, Yu CW, Velin D, Schneider P, Maslowski KM. Epithelial NAIPs protect against colonic tumorigenesis. J Exp Med. 2015;212:369-383

Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, Schilter HC, Rolph MS, Mackay F, Artis D, Xavier RJ, Teixeira MM, Mackay CR. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461:1282-1286.