Anti-CXCR2 directed therapy unmasks the potential for immunotherapy in pancreatic ductal adenocarcinoma
نویسندگان
چکیده
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy. Therapies targeted against stromal targets in the tumour microenvironment are now in pre-clinical and clinical trial. Here, we focus on our recent findings in autochthonous models of PDAC that suggest CXCR2 expressed on neutrophils is important in establishing immunosuppression in the primary tumour and the metastatic niche at distant sites. We discuss CXCR2 as a potential therapeutic target in the context of other potential stromal targets in PDAC.
منابع مشابه
CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma
CXCR2 has been suggested to have both tumor-promoting and tumor-suppressive properties. Here we show that CXCR2 signaling is upregulated in human pancreatic cancer, predominantly in neutrophil/myeloid-derived suppressor cells, but rarely in tumor cells. Genetic ablation or inhibition of CXCR2 abrogated metastasis, but only inhibition slowed tumorigenesis. Depletion of neutrophils/myeloid-derive...
متن کاملPrecision Immuno-Oncology: Prospects of Individualized Immunotherapy for Pancreatic Cancer
Pancreatic cancer, most commonly referring to pancreatic ductal adenocarcinoma (PDAC), remains one of the most deadly diseases, with very few effective therapies available. Emerging as a new modality of modern cancer treatments, immunotherapy has shown promises for various cancer types. Over the past decades, the potential of immunotherapy in eliciting clinical benefits in pancreatic cancer hav...
متن کاملMacrophage-based immunotherapy for the treatment of pancreatic ductal adenocarcinoma
Macrophages are critical proponents of the growth and development of pancreatic ductal adenocarcinoma. However, if properly instructed, macrophages can acquire anti-tumor properties, including the capacity to degrade the fibrous matrix that surrounds neoplastic lesions and to eliminate malignant cells, eventually leading to tumor regression.
متن کاملRelA regulates CXCL1/CXCR2-dependent oncogene-induced senescence in murine Kras-driven pancreatic carcinogenesis.
Tumor suppression that is mediated by oncogene-induced senescence (OIS) is considered to function as a safeguard during development of pancreatic ductal adenocarcinoma (PDAC). However, the mechanisms that regulate OIS in PDAC are poorly understood. Here, we have determined that nuclear RelA reinforces OIS to inhibit carcinogenesis in the Kras mouse model of PDAC. Inactivation of RelA accelerate...
متن کاملTumor-Induced IL-6 Reprograms Host Metabolism to Suppress Anti-tumor Immunity
In patients with cancer, the wasting syndrome, cachexia, is associated with caloric deficiency. Here, we describe tumor-induced alterations of the host metabolic response to caloric deficiency that cause intratumoral immune suppression. In pre-cachectic mice with transplanted colorectal cancer or autochthonous pancreatic ductal adenocarcinoma (PDA), we find that IL-6 reduces the hepatic ketogen...
متن کامل