Abstract SY25-03: From the clinic to the lab: Investigating response and resistance mechanisms to immune checkpoint therapy

Abstract

Abstract Immune checkpoint therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1, have led to significant clinical responses in cancer patients. To investigate immunologic changes and mechanistic pathways that are elicited by these therapies, we conducted presurgical and tissue-based clinical trials, which permit access to tumor tissues for laboratory studies. To compare and contrast data, we chose one tumor type that responds well to immune checkpoint therapy and one that does not. The first presurgical trial was conducted with anti-CTLA-4 (ipilimumab) in a cohort of patients with localized bladder cancer. The second presurgical trial was conducted with anti-CTLA-4 (ipilimumab) in patients with localized prostate cancer. In addition, we evaluated data from patients with melanoma who received immune checkpoint therapy. These data enabled us to identify the ICOS/ICOSL pathway as relevant for antitumor immune responses in the setting of anti-CTLA-4 therapy. We also identified resistance mechanisms, including expression of other immune inhibitory pathways such as VISTA and loss of the IFNγ signaling pathway in tumor cells. These data will be discussed in greater detail. Citation Format: Padmanee Sharma. From the clinic to the lab: Investigating response and resistance mechanisms to immune checkpoint therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY25-03. doi:10.1158/1538-7445.AM2017-SY25-03