From the Clinic to the Lab: Investigating Immune Responses to Immune Checkpoint Therapies
The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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 pre-surgical clinical trials, which permit access to sufficient tumor tissues for laboratory studies. The first pre-surgical trial was conducted with anti-CTLA-4 (ipilimumab) in a cohort of patients with localized bladder cancer. This trial provided access to sufficient tumor-infiltrating lymphocytes to conduct phenotypic and functional studies on these cells, which indicated the ICOS/ICOSL pathway as relevant for anti-tumor immune responses in the setting of anti-CTLA-4 therapy. In addition, since standard agents that enable tumor cell death may allow for priming of a T cell immune response that can be augmented by combination with CTLA-4 blockade, we conducted a pre-surgical clinical trial with androgen deprivation (hormonal) therapy ADT+ anti-CTLA-4 (ipilimumab), in the setting of patients with regional, high-risk prostate cancer. These pre-surgical clinical trials, and other tissue-based clinical trials, led to the identification of biomarkers and additional targets. These data, which are being used to design future immunotherapy trials, will be discussed in greater details.
Citation Format: Padmanee Sharma. From the clinic to the lab: Investigating immune responses to immune checkpoint therapies. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016; 76(3 Suppl): Abstract nr IA03.