Single-Cell Immune Competency Signatures Associate with Survival in Phase II GVAX and CRS-207 Randomized Studies in Patients with Metastatic Pancreatic Cancer
- 1 May 2020
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Immunology Research
- Vol. 8 (5), 609-617
- https://doi.org/10.1158/2326-6066.cir-19-0650
Abstract
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 patients with metastatic pancreatic cancer who were enrolled in two phase II 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 IIa patient subcohort (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 overall survival, range (days) 271, 43–1,247] compared with patients with a lower abundance of CD8+CD45RO−CCR7−CD57+ cells and higher abundance of CD14+CD33+CD85j+ cells (77, 24–1,247 days; P = 0.0442). The results from this prospective–retrospective biomarker analysis were validated by flow cytometry in 200 patients with pancreatic cancer enrolled in a phase IIb study (P = 0.0047). The identified immune correlates provide potential prognostic or predictive signatures that could be employed for patient stratification.Keywords
Other Versions
Funding Information
- NA
This publication has 25 references indexed in Scilit:
- Algorithmic Tools for Mining High-Dimensional Cytometry DataThe Journal of Immunology, 2015
- Safety and Survival With GVAX Pancreas Prime and Listeria Monocytogenes–Expressing Mesothelin (CRS-207) Boost Vaccines for Metastatic Pancreatic CancerJournal of Clinical Oncology, 2015
- Myeloid-derived suppressor cells in pancreatic cancer: more than a hidden barrier for antitumour immunity?Gut, 2014
- Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumabCancer Immunology, Immunotherapy, 2013
- CD8+ CD28− and CD8+ CD57+ T cells and their role in health and diseaseImmunology, 2011
- CD28−CD8+ T cells do not contain unique clonotypes and are therefore dispensableImmunology Letters, 2009
- Cryopreservation Decreases Receptor PD-1 and Ligand PD-L1 Coinhibitory Expression on Peripheral Blood Mononuclear Cell-Derived T Cells and MonocytesClinical and Vaccine Immunology, 2009
- Listeria-based cancer vaccines that segregate immunogenicity from toxicityProceedings of the National Academy of Sciences of the United States of America, 2004
- HIV infection and aging: enhanced Interferon- and Tumor Necrosis Factor-alpha production by the CD8+ CD28- T subsetBMC Immunology, 2001
- Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial.Journal of Clinical Oncology, 1997