Increased frequency of CCR7(+) CD4(+) T cells from patients with primary Sjogren's syndrome: An indicator of disease activity rather than of damage severity
CYTOKINE
Authors: Wu, Chunling; Yang, Pingting; Liu, Haina; Xiao, Weiguo; Zhao, Lijuan
Abstract
Expression of CCR7 on T cells has been reported to be associated with the lymphocytic migration and infiltration, which is recognized as a vital part of the pathogenesis of Primary Sjogren's syndrome (pSS). Here, we compared the expression of CCR7 on CD4 + T cells between pSS patients and control groups, including healthy donors (HD) and patients with systemic lupus erythematosus (SLE) and examined correlations with disease activity and damage severity, which were evaluated by EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) and Sjogren's Syndrome Disease Damage Index (SSDDI), respectively. Peripheral blood mononuclear Cells (PBMC) were obtained from patients and controls and expressions of CCR7 were evaluated by flow cytometry. CCR7 was selectively and frequently expressed on CD4 (+) T cells, but less on CD8 (+) T cells of patients with pSS. In contrast, this phenomenon was neither seen in normal subjects nor in patients with SLE. The expression level of CCR7 in the peripheral blood CD4 (+) T cells is closely correlated with ESSDAI, but not SSDDI. Correspondently, the chemotactic index (CI) of CD4(+)T cells was higher than CD8-FT cells in patients with pSS. Furthermore, the CI of CD4(+)T cells is also higher than that of other controls, which is correlated with ESSDAI. All the findings suggested that CCR7 might play an important role in the development of pSS by mediating the migration of CD4(+) cells. Thus, the expression of CCR7 in CD4 (+) T cells is probably a useful biomarker to evaluate and monitor disease activity. CCR7 can also potentially be a novel target for the therapy of pSS.
Single-Cell Immune Competency Signatures Associate with Survival in Phase II GVAX and CRS-207 Randomized Studies in Patients with Metastatic Pancreatic Cancer
CANCER IMMUNOLOGY RESEARCH
Authors: Nair, Nitya; Chen, Shih-Yu; Lemmens, Ed; Chang, Serena; Le, Dung T.; Jaffee, Elizabeth M.; Murphy, Aimee; Whiting, Chan; Mueller, Thomas; Brockstedt, Dirk G.
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.