Abstract

PURPOSE: Resistance to anti-PD1 based immune checkpoint blockade (ICB) remains a problem for the treatment of metastatic melanoma. Tumor cells as well as host myeloid cells can express the immune checkpoint ligand CD155 to regulate immune cell function. However, the effect of tumor CD155 on the immune context of human melanoma has not been well described. This observational study characterizes tumor CD155 ligand expression by metastatic melanoma tumors and correlates results with differences in immune cell features and response to ICB. EXPERIMENTAL DESIGN: Pre-treatment tumor specimens, from 155 metastatic melanoma patients treated with ICB and from 50 patients treated with BRAF/MEK-directed-targeted therapy, were assessed for CD155 expression by immunohistochemistry. Intratumor T cell features were analysed using multiplex-immunohistofluorescence for CD8, PD1 and SOX10. Correlations were made between CD155 tumor level and bulk tumor RNA-seq results, as well as clinical RECIST response and progression-free survival. RESULTS: ) and poor response to anti-PD1 therapy. In PD-L1 negative tumors, high CD155 tumor expression was associated with patients who had poor response to combination anti-PD1/CTLA4 therapy. CONCLUSIONS: T cells in anti-PD1 refractory melanoma tumors and, further, that targeting the CD155 pathway might improve response to anti-PD1 therapy for metastatic melanoma patients.

Authors	Lepletier, Ailin; Madore, Jason; O'Donnell, Jake S; Johnston, Rebecca L; Li, Xian-Yang; McDonald, Elizabeth; Ahern, Elizabeth; Kuchel, Anna; Eastgate, Melissa; Pearson, Sally-Ann; Mallardo, Domenico; Ascierto, Paolo A; Massi, Daniela; Merelli, Barbara; Mandala, Mario; Wilmott, James S; Menzies, Alexander M; Leduc, Charles; Stagg, John; Routy, Bertrand; Long, Georgina V; Scolyer, Richard A; Bald, Tobias; Waddell, Nicola; Dougall, William C; Teng, Michele W L; Smyth, Mark J
Journal	CLINICAL CANCER RESEARCH
Pages	3671-3681
Volume	26
Date	1/04/2020
Grant ID
Funding Body	BristolMyers Squibb
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1158/1078-0432.CCR-19-3925
	Download Article