Myeloid innate immunity

Programme stream(s): Cancer discovery / underpinning research
Programme session type(s): Specialist session

Chair: Jeffrey Pollard, University of Edinburgh, UK
Speaker: Michael Schmid, University of Liverpool, UK
Speaker: Fran Balkwill, Barts Cancer Institute, UK
Speaker: Miki De Palma, Swiss Institute for Experimental Cancer Research, Switzerland

14:00-16:00

Room: Dochart

Despite the increasing success of novel cancer immunotherapies (ITX), unfortunately a substantial number of patients do not benefit from these therapies as they do not respond or develop resistance. Recent studies in disease models and patients have identified myeloid cells with immunoregulatory activity (MRCs) in the tumor microenvironment (TME) as a key player limiting anti-tumor immunity and the efficacy of modern ITXs. These cells are mostly myeloid in origin and therefore can be targeted to improve therapy. This session will present data on their pro-tumoral activities and ways to target or reverse these functions. By the end of the session participants will learn the definitions of myeloid cells in the TME and their pro-tumoral phenotypes. Therapeutics to target them will be explained and the drawbacks considered. Combination therapies with ITX will also be discussed.

Myeloid cells in the ovarian cancer microenvironment
Speaker: Fran Balkwill
Affiliation: Barts Cancer Institute

Abstract:

Much of our work focuses on understanding and targeting the tumour microenvironment, TME, of high-grade serous ovarian cancer, HGSOC. We aim to find ways to eradicate the peritoneal metastases that arise early in this disease, recur after chemotherapy and are ultimately lethal. We are using our extensive knowledge of human HGSOC metastases and a platform of clinically relevant mouse and human models that replicate the genetics and TME of the human cancer.

Macrophages: Bad Actors in Cancer
Speaker: Jeffrey Pollard
Affiliation: The University of Edinburgh

Abstract:

The majority of deaths caused by cancer are due to metastasis. This fact indicates that metastatic tumours are resistant to available therapies. Tumors consist not only of malignant cells but also a wide-range of non-mutated normal cells including those of the immune system.  Among these immune cells, macrophages are particularly abundant in a wide range of tumors. Our studies focussing on breast cancer have indicated that macrophages promote tumor progression to malignancy in mouse models.  Recently we have identified a sub-population of metastasis-associated macrophages (MAM) that help metastatic tumour cells seed at distant sites and prosper. Lineage tracking indicates that MAMs derive from the Ly6Chi population of circulating monocytes that are recruited by tumour cell produced chemokine CCL2 at the metastatic site. CCL2 signals via CCR2 in the monocytes to upregulate expression of CCL3 that in turn binds to CCR1 in an autocrine manner. This signaling pathway results in the retention of the monocytes and their differentiation into MAMs that then deliver a survival signal to the tumour cells. Differentiation of the monocytes to MAMs involves several intermediate steps whereby these cells also attain immunosuppressive phenotypes against activated T cells. Inhibition of any of these steps of MAM recruitment or differentiation using genetic or inhibitor approaches reduces metastasis in these mouse models. Such data suggest that therapeutics directed against the pro-tumoral functions of these myeloid cells might become part of a strategy that will improve survival of patients with metastatic disease.