CD16/complement-expressing macrophages are critical to immunotherapy response in melanoma | Dr James Wilmott

CD16+/C1qa expressing macrophages are a critical component of immune responses to anti-PD-1 monotherapy and anti-PD-1/anti-CTLA-4 combination immunotherapies in melanoma patients.

29 July 2020

Dr James Wilmott
NHMRC Investigator Fellow
Translational Melanoma Research Group, Melanoma Institute Australia
The University of Sydney

The role of innate immune cell populations in determining the response of cancer patients to immunotherapies remains unclear. Dr Wilmott and group characterised tumour infiltrating macrophages in biopsies of advanced melanoma patients treated with either anti-PD-1 monotherapy or combination anti-PD1/anti-CTLA4 ICI (n=115). They demonstrate that CD16+ intratumoral macrophage are associated with increased expression of the chemoattractant CXCL10, CXCL11 and CXCL13, cytotoxic T-cell infiltration and response to both anti-PD1 and anti-PD1/anti-CTLA4 ICI.

Single-cell transcriptomics analysis of identified increased expression of the classical complement pathway in CD16+ macrophages, which was confirmed in FACS analysis of tumour dissociates. Subsequent tissue-based analysis identified that CD16+, complement expressing macrophages exclusively express PD-1, with these populations increasing following treatment with anti-PD-1 ICI. Our study highlights that CD16+ macrophages are the major complement engaging immune cells, expression of receptors with affinity to both anti-PD-1 and anti-CTLA-4 and form a critical component of the immune response to these ICI therapies.

Senior lecturer James Wilmott is the research leader of the Translational Melanoma Research Group of the Melanoma Institute Australia, The University of Sydney. Dr Wilmott is a current holder of an NHMRC early career fellowship and received his PhD in 2013 from the University of Sydney.

Dr Wilmott is recognised internationally as an emerging expert in clinical implications of genomic profiles (First author Nature and Int J Cancer), immune profiling of cancer tissue (Co-author in Nature, The Lancet Oncology, senior author in Clinical Cancer Research and Oncoimmunology) and in biomarkers of response of systemic therapies (Senior author Cancer Cell).