LPS and IL-8 activated umbilical cord blood-derived neutrophils inhibit the progression of ovarian cancer

Abstract

Background: Immunotherapy including immune checkpoint blockade, cancer vaccines, and adoptive cell therapy. However, no immune therapies support ovarian cancer. It is not clear whether the neutrophils, the component of the immune system derived from umbilical cord blood play a role in inhibiting the progression of ovarian cancer. Methods: We investigate the impact of LPS and IL-8 activated neutrophils derived from umbilical cord blood(UCB)on ovarian cancer progression. After co-culture LPS and IL-8 activated UCB-derived neutrophils with ovarian cancer cell line SKOV3 and OVCAR3, CCK8, Transwell assay, and Flow Cytometry was performed to detect cell proliferation, migration, invasion, and apoptosis of ovarian cancer cell lines SKOV3 and OVCAR3. Furthermore, RT-PCR and western blotting assay were used to analyze the mechanism of metastasis and apoptosis of ovarian cancer cell lines respectively to support previous function experiments. Results: We demonstrate LPS and IL-8 activated neutrophils derived from umbilical cord blood inhibit proliferation, invasion migration and promote apoptosis of SKOV3 and OVCAR3. Meanwhile, LPS and IL-8 activated UCB-derived neutrophils significantly decreased BAX and increased BCL2 expression in SKOV3 and OVCAR3 which account for the mechanism of apoptosis. Moreover, LPS and IL-8 activated UCB derived neutrophils significantly up-regulated E-cadherin and downregulated N-cadherin, MMP2 expression in SKOV3 and OVCAR3. Conclusion: Taken together, these results approved that LPS and IL-8 activated neutrophils from UCB may be the novel strategy in immune therapy for ovarian cancer.

Primitive genotypic characteristics in umbilical cord neutrophils identified by single-cell transcriptome profiling and functional prediction

“…Granulocyte transfusion as one of the main treatment methods has a long history in treating patients with neutropenia or neutrophilic dysfunction, and can be used to prevent and treat infection ( 4 ). In addition, in recent years, with the emergence of immunotherapy, neutrophilic adoptive therapy also began to be used in the treatment of refractory infectious diseases and malignant tumors, and good therapeutic effect was achieved ( 5 ).…”

Recombinant Lactococcus Expressing a Novel Variant of Infectious Bursal Disease Virus VP2 Protein Can Induce Unique Specific Neutralizing Antibodies in Chickens and Provide Complete Protection

“…The proliferative activity of PBMCs stimulated with Lipopolysaccharide (LPS) was measured as described previously [43]. PBMC was diluted to 1 × 10 6 cells/mL with RPMI 1640 culture medium containing 10% fetal bovine serum (Gibco, Gaithersburg, MD, USA) and penicillin-streptomycin (Wisent, Saint-Jean-Baptiste, QC, Canada).…”

A novel tumor-immune microenvironment (TIME)-on-Chip mimics three dimensional neutrophil-tumor dynamics and neutrophil extracellular traps (NETs)-mediated collective tumor invasion

“…Conversely, chemotherapy induced neutropenia has also predicted improved survival rates among cancer patients [12][13][14][15][16][17], thereby raising important questions on the impact of neutrophils in tumor development. In the context of tumor metastasis, research has produced conflicting data in explaining whether neutrophils could promote the metastatic cascade [18][19][20][21][22], or support immune reactions inhibiting tumor growth [23][24][25][26]. A fuller understanding of the multifaceted neutrophil functionalities in tumorigenesis is still evolving [27], but there is a steadily growing appreciation that neutrophils can provide critical insights that are essential to tailor suitable anti-tumor and immunotherapeutic strategies, complementary to current therapeutic approaches [4,[28][29][30].…”