Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer
Systemic failure remains a challenge in rectal cancer. We investigated the possible systemic anti-tumour immune activity invoked within oxaliplatin-based neoadjuvant therapy. In two high-risk patient cohorts, we assessed the circulating levels of the fms-like tyrosine kinase 3 ligand (Flt3L), a factor reflecting both therapy-induced myelosuppression and activation of tumour antigen-presenting dendritic cells, at baseline and following induction chemotherapy and sequential chemoradiotherapy, both modalities containing oxaliplatin. The primary end point was progression-free survival (PFS). In both cohorts, the median Flt3L level was significantly higher at completion of each sequential modality than at baseline. The 5-year PFS (most events being metastatic progression) was 68% and 71% in the two cohorts consisting of 33% and 52% T4 cases. In the principal cohort, a high Flt3L level following the induction chemotherapy was associated with low risk for a PFS event (HR: 0.15; P < 0.01). These patients also had available dose scheduling and toxicity data, revealing that oxaliplatin dose reduction during chemoradiotherapy, undertaken to maintain compliance to the radiotherapy protocol, was associated with advantageous PFS (HR: 0.47; P = 0.046). In high-risk rectal cancer, oxaliplatin-containing neoadjuvant therapy may promote an immune response that favours survival without metastatic progression.
Erta Kalanxhi; Sebastian Meltzer; Jakob Vasehus Schou; Finn Ole Larsen; Svein Dueland; Kjersti Flatmark; Benny Vittrup Jensen; Knut Håkon Hole; Therese Seierstad; Kathrine Røe Redalen; Dorte Lisbet Nielsen; Anne Hansen Ree
Response to 'Evolving M-protein pattern in patients with smoldering multiple myeloma: impact on early progression'
Response to 'Evolving M-protein pattern in patients with smoldering multiple myeloma: impact on early progression', Published online: 25 May 2018; doi:10.1038/s41375-018-0155- ... more
Coppery inks paint an underwater rainbow
Coppery inks paint an underwater rainbow, Published online: 25 May 2018; doi:10.1038/d41586-018-05282-y
Inexpensive version of luminescent pigment shrugs off water. more
Previous studies suggested that MeCP2 competes with linker histone H1, but this hypothesis has never been tested in vivo. Here, we performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) of Flag-tagged-H1.0 in mouse forebrain excitatory neurons. Unexpectedly, Flag-H1.0 and ... more
Olympus Microscopy has partnered with the Nature Publishing Group to present the Neurotechniques Collection. This compilation of articles will draw together some of the groundbreaking research that has recently been published in Nature Reviews Neuroscience and Nature Methods. Sponsored by O ... more