Photodynamic Therapy-mediated Cancer Vaccination Enhances Stem-like Phenotype and Immune Escape, Which Can Be Blocked by Thrombospondin-1 Signaling through CD47 Receptor Protein

Abstract

Background: Photodynamic therapy (PDT)-mediated vaccination has shown poor clinical outcomes in tumor treatment. Results: Tumor cells that escaped from PDT-mediated vaccination exhibited enhanced stem-like phenotypes and undermined immunogenicity, which were prevented by interfering TSP-1/CD47/SIRP-␣ signal axis. Conclusion: TSP-1/CD47/SIRP-␣ signal axis is associated with the malignant evolution of tumor cells upon tumor vaccination. Significance: This study provides new evidence for improving the clinical outcome of immunotherapy.

Inhibition of polypyrimidine tract-binding protein 3 induces apoptosis and cell cycle arrest, and enhances the cytotoxicity of 5- fluorouracil in gastric cancer cells

“…PTB-targeting pSilencer plasmid was constructed as described in the previous report (Zheng et al , 2015). Briefly, p Silencer 2.1-U6 Neo vector and the non-targeting control plasmid were purchased from Invitrogen.…”

Thrombospondin promoted anti-tumor of adenovirus-mediated calreticulin in breast cancer: Relationship with anti-CD47

“…As one of several functions, CD47 serves as the ligand for TSP 294 that expressed on the surface of phagocytic cells, including 295 macrophages and dendritic cells [19,20]. The interaction of 296 CD47 and TSP initiates a signal transduction cascade, resulting 297…”

Divergent modulation of normal and neoplastic stem cells by thrombospondin-1 and CD47 signaling

“…Repeated passage in immune-competent mice to select resistant cells from Lewis lung carcinoma resulted in the isolation of cells with increased CSC characteristics as well as increased CD47 expression (Zheng et al, 2015). Notably, the selected cells also had very low TSP1 expression.…”

“…Notably, knockdown of CD47 using a shRNA vector blocked these responses to TSP1. TSP1 treatment also inhibited proliferation and suppressed sphere formation in human colon cancer (HCT116), non-small cell lung cancer (A549), and cervical cancer (HeLa) cell lines (Zheng, 2015). These data further support a cell-autonomous function of CD47 signaling in CSCs and implicate TSP1 signaling through CD47 in regulating CSC fate.…”

“…We have shown that Burkitt’s lymphoma cells, where the 5’ promoter region of cMyc is replaced with Ig heavy chain promoter sequence, are resistant to growth inhibition by CD47 over-expression, and cMyc expression is unperturbed by CD47 in these cells (Kaur, 2013). Others have identified NFκB dependent regulation of cystatin-S/protease activated receptor-2, p21, Gβγ-dependent activation of the PI3-kinase/Akt pathway, and ubiquitin-like with PHD and ring finger domains 1 (UHRF1)-dependent down-regulation of p16 INK4A as targets of CD47 signaling in specific cancer cell lines (Boukhari et al, 2015; Lee, 2014b; Sick et al, 2011; Zheng, 2015). Further study is needed to determine which of these CD47 target pathways generalize to other cancer types, and which may differ in neoplastic versus nontransformed stem cells.…”