12 research outputs found
Circulating neutrophils and tumor-associated myeloid cells function as a powerful biomarker for response to chemoradiation in locally advanced cervical cancer
Purpose: The immune system’s role in mediating the cytotoxic effects of chemoradiotherapy remains not completely understood. The integration of immunotherapies into treatment will require insight into features and timing of the immune microenvironment associated with treatment response. Here, we investigated the role of circulating neutrophils and tumor-associated myeloid cells (TSAMs) as potential agents and biomarkers for disease-related outcomes in locally advanced cervical cancer (LACC). Material and Methods: Hematologic parameters for two LACC patient cohorts, a retrospective clinical and a prospective translational cohort, were obtained at baseline, weekly during chemoradiotherapy for the retrospective cohort, biweekly during chemoradiotherapy for the prospective cohort, and at the first follow-up visit for both cohorts (mean 14.7 weeks, range 8.1–25.1 weeks for the prospective cohort and 5.3 weeks with a range of 2.7–9.0 weeks for the retrospective cohort). In both cohorts, baseline as well as mean and lowest on-treatment values for platelets, hemoglobin, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) were analyzed for correlations with disease-related outcomes. In the prospective cohort, circulating myeloid cells were isolated from peripheral blood mononuclear cells (PBMCs), and TSAMs were isolated from tumor tissue via a novel serial cytobrush sampling assay. The samples were analyzed by flow cytometry. Results: In both cohorts, the only hematologic parameter significantly associated with survival was elevated on-treatment mean ANC (mANC), which was associated with lower local failure-free and overall survival rates in the retrospective and prospective cohorts, respectively. mANC was not associated with a difference in distant metastases. CD11b+CD11c- TSAMs, which act as a surrogate marker for intratumoral neutrophils, steadily decreased during the course of chemoRT and nadier’d at week 5 of treatment. Conversely, circulating myeloid cells identified from PBMCs steadily increased through week 5 of treatment. Regression analysis confirmed an inverse relationship between circulating myeloid cells and TSAMs at this time point. Conclusions: These findings identify on-treatment mean neutrophil count as a predictor of disease-related outcomes, suggest that neutrophils contribute to chemoradiation treatment resistance, and demonstrate the importance of techniques to measure intratumoral immune activity
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Evidence of Local Extinction and Reintroduction of Aedes aegypti in Exeter, California
Established populations of Aedes aegypti, a mosquito vector of multiple major arthropod-borne viruses, were first found in three California (CA) cities in 2013. From 2013 to April 2021, Ae. aegypti thwarted almost all control efforts to stop its spread and expanded its range to 308 cities, including Exeter, in 22 counties in CA. Population genomic analyses have suggested that multiple genetically distinct Ae. aegypti populations were introduced into CA. However Ae. aegypti collected for the first time in 2014 in Exeter, appeared to be different from three major genetic clusters found elsewhere in CA. Due to intense control efforts by the Delta Vector Control District (DVCD), Ae. aegypti was thought to have been eliminated from Exeter in 2015. Unfortunately, it was recollected in 2018. It was not clear if the reemergence of Ae. aegypti in Exeter was derived from the bottlenecked remnants of the original 2014 Exeter population or from an independent invasion from a different population derived from surrounding areas. The goal of this work was to determine which of these scenarios occurred (recovery after bottleneck or reintroduction after elimination) and if elimination and reintroduction occurred to identify the origin of the invading population using a population genomic approach. Our results support the reintroduction after elimination hypothesis. The source of reintroduction, however, was unexpectedly from the southern CA cluster rather than from other two geographically closer central CA genetic clusters. We also conducted a knockdown resistance mutation profile, which showed Exeter 2014 had the lowest level of resistant alleles compared to the other populations, could have contributed towards DVCD’s ability to locally eliminate Ae. aegypti in 2014