0000000000109669
AUTHOR
Lucia Sfondrini
Additional file 2: of The PDGFRβ/ERK1/2 pathway regulates CDCP1 expression in triple-negative breast cancer
Figure S2. PDGFR-BB stimulation upregulates CDCP1 in TNBC cells. Western blot analysis of CDCP1 and Vinculin expression in SUM-149 and BT549 cells upon PDGF-BB and ERKi treatment. (PDF 249 kb)
Anti-tumor activity of CpG-ODN aerosol in mouse lung metastases
Studies in preclinical models have demonstrated the superior anti-tumor effect of CpG oligodeoxynucleotides (CpG-ODN) when administered at the tumor site rather than systemically. We evaluated the effect of aerosolized CpG-ODN on lung metastases in mice injected with immunogenic N202.1A mammary carcinoma cells or weakly immunogenic B16 melanoma cells. Upon reaching the bronchoalveolar space, aerosolized CpG-ODN activated a local immune response, as indicated by production of IL-12p40, IFN-γ and IL-1β and by recruitment and maturation of DC cells in bronchoalveolar lavage fluid of mice. Treatment with aerosolized CpG-ODN induced an expansion of CD4+ cells in lung and was more efficacious tha…
Toll Like Receptors as Sensors of the Tumor Microbial Dysbiosis: Implications in Cancer Progression
Microbiota is a complex ecosystem of active microorganisms resident in the body of mammals. Although the majority of these microorganisms resides at the distal gastrointestinal tract, high-throughput DNA sequencing technology have made possible to understand that several other tissues of the human body host their own microbiota, even those once considered sterile, such as lung tissue. These bacterial communities have important functions in maintaining a healthy body state and the host immune system has evolved multiple mechanisms by which maintaining a symbiotic relationship with the microbiota. The maintenance of this dialogue allows the induction of protective responses to pathogens and r…
Additional file 1: of The PDGFRβ/ERK1/2 pathway regulates CDCP1 expression in triple-negative breast cancer
Figure S1. Gating strategy for CDCP1 flow cytometric analysis. Flow cytometric analysis of MDA-MB-231 cells starved in serum-free medium for 24 h and then treated for 48 h with FGF 50 ng/mL. (PDF 470 kb)
The PDGFRβ/ERK1/2 pathway regulates CDCP1 expression in triple-negative breast cancer
Background CDCP1, a transmembrane protein with tumor pro-metastatic activity, was recently identified as a prognostic marker in TNBC, the most aggressive breast cancer subtype still lacking an effective molecular targeted therapy. The mechanisms driving CDCP1 over-expression are not fully understood, although several stimuli derived from tumor microenvironment, such as factors present in Wound Healing Fluids (WHFs), reportedly increase CDCP1 levels. Methods The expression of CDCP1, PDGFRβ and ERK1/2cell was tested by Western blot after stimulation of MDA-MB-231 cells with PDGF-BB and, similarly, in presence or not of ERK1/2 inhibitor in a panel of TNBC cell lines. Knock-down of PDGFRβ was e…
Poly(I:C) and CpG-ODN combined aerosolization to treat lung metastases and counter the immunosuppressive microenvironment.
The immunostimulatory ability of synthetic oligonucleotides containing CpG motifs (CpG-ODN), agonists of Toll-like receptor 9 (TLR9), can be harnessed to promote antitumor immunity by their application at the tumor site to stimulate local activation of innate immunity; however, particularly in the lung, tumor-associated immunosuppression can subvert such antitumor innate immune responses. To locally maintain continuous activation of innate subpopulations while inhibiting immunosuppressive cells, we evaluated aerosol delivery CpG-ODN combined with Poly(I:C), a TLR3 agonist able to convert tumor-supporting macrophages to tumoricidal effectors, in the treatment of B16 melanoma lung metastases …
Antibody–Fc/FcR Interaction on Macrophages as a Mechanism for Hyperprogressive Disease in Non–small Cell Lung Cancer Subsequent to PD-1/PD-L1 Blockade
Abstract Purpose: Hyperprogression (HP), a paradoxical boost in tumor growth, was described in a subset of patients treated with immune checkpoint inhibitors (ICI). Neither clinicopathologic features nor biological mechanisms associated with HP have been identified. Experimental Design: Among 187 patients with non–small cell lung cancer (NSCLC) treated with ICI at our institute, cases with HP were identified according to clinical and radiologic criteria. Baseline histologic samples from patients treated with ICI were evaluated by IHC for myeloid and lymphoid markers. T-cell–deficient mice, injected with human lung cancer cells and patient-derived xenografts (PDX) belonging to specific mutat…