The transformative impact of cancer immunotherapy has been accompanied by an equally daunting realization of its inherent limitations, including intrinsic and acquired resistance. These shortcomings have highlighted the acute need to understand host factors influencing immunotherapy sensitivity and to develop predictive metrics of initial patient response. In particular, the host microbiome is believed to strongly influence immunotherapeutic efficacy, while advances in organoid technologies present novel opportunities for tumor immune response modeling. This team seeks to address these needs through the integration of microbiome and organoid analyses of patient cohorts receiving anti-PD(L)1-based immunotherapies, leading to the derivation of novel immunooncology therapeutics.
In Aim 1, the team will perform microbiome analysis and organoid modeling of a neoadjuvant anti- PD(L)1 metastatic melanoma cohort from the large volume of patients treated at MD Anderson.
Aim 2 mines pre-existing anti-PD(L)1 clinical cohorts for microbiota composition and secreted bioactive small molecule and small peptide signatures, which will be modeled in organoids.
Aim 3 exploits Aims 1 and 2 to develop microbiota-based enhancers of immunotherapy.