Single-cell immune competency signatures associate with survival in phase 2 GVAX and CRS-207 randomized studies in metastatic pancreatic cancer patients
Nair, N., Chen, S-Y., Lemmens, E. et al.The identification of biomarkers for patient stratification is fundamental to precision medicine efforts in oncology. Here, we identified two baseline, circulating immune cell subsets associated with overall survival in metastatic pancreatic cancer patients who were enrolled in two phase 2 randomized studies of GVAX pancreas and CRS-207 immunotherapy. Single-cell mass cytometry was used to simultaneously measure 38 cell surface or intracellular markers in peripheral blood mononuclear cells obtained from a phase 2a patient sub-cohort (N=38). CITRUS, an algorithm for identification of stratifying subpopulations in multidimensional cytometry datasets, was used to identify single-cell signatures associated with clinical outcome. Patients with a higher abundance of CD8+CD45RO-CCR7-CD57+ cells and a lower abundance of CD14+CD33+CD85j+ cells had improved overall survival (median OS, range (days) 271, 43-1247) compared to patients with a lower abundance of CD8+CD45RO-CCR7-CD57+ cells and higher abundance of CD14+CD33+CD85j+ cells (77, 24-1247 days; P=0.0442). The results from this prospective-retrospective biomarker analysis were validated by flow cytometry in 200 pancreatic cancer patients enrolled in a phase 2b study (P=0.0047). The identified immune correlates provide potential prognostic or predictive signatures that could be employed for patient stratification.
Nair, N., Chen, S-Y., Lemmens, E. et al. "Single-cell immune competency signatures associate with survival in phase 2 GVAX and CRS-207 randomized studies in metastatic pancreatic cancer patients" Cancer Immunology Research (2020): 609–17