Abstract 3246: Dynamics of T-cell checkpoint receptor profiles during melanoma progression

Abstract

Abstract Background A myriad of novel monoclonal antibody based immunotherapies targeting co-stimulating and co-inhibitory receptors have entered clinical trials in melanoma with the aim of increasing response rates and overcoming resistance to standard anti-CTLA-4 and anti-PD-1 immunotherapy. However, little is known about the abundance, co-expression and immune cells enriched for each specific drug target in the various stages of melanoma progression. Therefore, we sought to assess the relative abundance of checkpoint receptors and their expression during melanoma disease progression, as well as the immune cells enriched for each of these molecules. Methods - Multiplex immunofluorescence staining for immune checkpoint receptors (ICOS, GITR, OX40, PD-1, TIM-3, and VISTA) was performed on 95 melanoma biopsies from 41 melanoma patients, including patient matched biopsies for primary, regional lymph node or distant metastases. - Mass cytometry was performed on leukocytes isolated from 18 treatment-naïve melanoma tumors to explore immune subsets enriched for many of the checkpoint receptors currently targeted in clinical trials. Results & Conclusions GITR and OX40 were the least abundant checkpoint receptors in melanoma (p<0.001), with less than 1% of intra-tumoral T cells expressing either marker. TIM-3 and VISTA were mostly expressed on non-T cell populations, with TIM-3 enriched on dendritic cells. Tissue resident T cells (CD69+ CD103+ CD8+) represented a population highly enriched for TIGIT (>70%) and other co-inhibitory receptors but not co-stimulatory receptors. The proportion of GITR+ T cells decreases from primary melanoma (>5%) to patient matched lymph node (<1%, p=0.04) and distant metastases (<1%, p=0.0005). This data will underpin future clinical trial design and provide a rationale for combining these molecules in the clinic. Note: This abstract was not presented at the meeting. Citation Format: Jarem Edwards, Annie Tasker, Inês Pires da Silva, Camelia Quek, Benjamin M. Allanson, Robyn P. M Saw, John F. Thompson, Alexander M. Menzies, Umaimainthan Palendira, James S. Wilmott, Georgina V. Long, Richard Scolyer. Dynamics of T-cell checkpoint receptor profiles during melanoma progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3246.