Background: Tumor-related leukocytosis (TRL) is occasionally found in patients with nonhematopoietic malignancies. We investigated the clinical implication of TRL and individualized treatment for TRL-positive cervical cancer, as well as the underlying biological mechanism.
Methods: Clinical data from 258 cervical cancer patients treated with definitive radiotherapy were analyzed to investigate the association between TRL and treatment outcome. Clinical samples, cervical cancer cell lines, and a mouse model of cervical cancer were used to examine the mechanisms responsible for TRL in cervical cancer, focusing on the role of tumor-derived granulocyte colony-stimulating factor (G-CSF) and myeloid-derived suppressor cells (MDSCs). All statistical tests were two-sided.
Results: TRL was statistically significantly associated with younger age (Wilcoxon rank sum test, P = .03), larger tumor size (Wilcoxon rank sum test, P = .006), advanced clinical stage (χ(2) test, P = .01), and shorter overall survival (Cox proportional hazard modeling and Wald tests, P < .001). Among cervical cancer patients, TRL was associated with upregulated tumor G-CSF expression (χ(2) test, P < .001), elevated serum G-CSF levels (Student t test, P = .03), larger spleens (Student t test, P = .045), and increased MDSC frequencies in the blood (Student t test, P < .001) compared with the TRL-negative patients. In vitro and in vivo experiments revealed that tumor-derived G-CSF was involved in the underlying causative mechanism of TRL and MDSCs induced by tumor-derived G-CSF are responsible for the rapidly progressive and radioresistant nature of TRL-positive cervical cancer. The administration of anti-Gr-1 neutralizing antibody or the depletion of MDSCs by splenectomy (n = 6 per group) inhibited tumor growth and enhanced radiosensitivity in TRL-positive cervical cancer xenografts (Wilcoxon rank sum test, P = .008 and P = .02, respectively).
Conclusions: TRL is associated with resistance to radiotherapy among cervical cancer patients, and MDSC-targeting treatments may have therapeutic potential in these patients.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/jnci/dju147 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Editorial Expression of Concern: Control of PD-L1 expression by miR-140/142/340/383 and oncogenic activation of the OCT4-miR-18a pathway in cervical cancer.
Oncogene
January 2025
Department of Women's Health Educational System, Hokkaido University School of Medicine, Hokkaido University, Sapporo, 0608638, Japan.
Dual-OR Logic-Gated Lateral Flow Strip Assay Based on Colorimetric-Fluorescence Dual Indication for Screening of HPV16/18 in Multiple Scenarios.
Anal Chem
January 2025
Center of Clinical Laboratory Medicine, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, Jiangsu, China.
The incidence of cervical cancer continues to rise in underdeveloped regions due to low human papillomavirus (HPV) vaccination rates and inadequate screening systems. To achieve convenient, rapid, and accurate detection of HPV, we developed a three-wire lateral flow strip assay system based on dual-OR logic gates for rapid and simultaneous detection of HPV subtypes 16 and 18 in a single test. The system combines three-branch-catalytic hairpin assembly (TCHA)-mediated signal amplification with simple OR logic gate-based signal output to improve detection rates while enabling HPV 16/18 subtype identification.
View Article and Find Full Text PDFClinicopathological and prognostic significance of the microcystic elongated and fragmented pattern in endometrial cancer: a systematic review and meta-analysis.
BMJ Open
January 2025
Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China
Objective: The presence of the microcystic elongated and fragmented (MELF) pattern, distinguished by its microcystic, elongated and fragmented attributes, constitutes a common manifestation of myometrial invasion (MI) within endometrial carcinoma. However, the prognostic significance of this pattern has not been definitively established. Consequently, this research aimed to clarify the prognostic implications of the MELF pattern for individuals diagnosed with endometrial carcinoma.
View Article and Find Full Text PDFCobalt polygalacturonates and the pharmacological composition based on them: Preparation, properties and cytotoxicity.
Int J Biol Macromol
January 2025
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str. 8, Kazan, Russia.
The aim of the present study was to obtain new metal complexes of citrus pectin with cobalt ions based on potassium polygalacturonate and to prepare a new pharmacological composition (PC) PGKCo: PGNaCo (1:1) with antitumor activity based on potassium cobalt polygalacturonate (PGKCo) and sodium cobalt polygalacturonate (PGNaCo). The study of the effect of PGKCo, PGNaCo and PC on the cell viability of tumor cell lines of different genesis in vitro showed that the obtained compounds are soluble in water and exhibit selective cytotoxic activity against the tumor cell lines of human lung carcinoma A549, breast adenocarcinoma MCF-7 and cervical carcinoma M-HeLa, with no significant toxic effect on normal human cells. The possible mechanism of action of the investigated PC on M-HeLa cancer cells was investigated.
View Article and Find Full Text PDFRelationship between muscular mass, inflammatory status, tumor metabolic activity and oral intake in head and neck cancer at the outset of management.
Clin Nutr ESPEN
January 2025
Service d'orl et chirurgie cervico-faciale, CHU de Clermont-Ferrand, 58 rue Montalembert, 63000 Clermont-Ferrand, France; Unité de Nutrition Humaine (UNH), Université Clermont Auvergne, INRAE, CRNH Auvergne, 58 rue Montalembert, 63000 Clermont-Ferrand, France. Electronic address:
Background And Aims: Patients with head and neck cancer (HNC) are often malnourished with a low muscular mass at the outset of management. This is thought to be mainly due to poor nutritional intake. The aim of this study was to assess the correlation between tumor metabolic activity, inflammatory status and body composition in HNC patients.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!