Envisioning the immune system to determine its role in pancreatic ductal adenocarcinoma: Culprit or victim?

Pancreatic ductal adenocarcinoma has a poor 5-year survival rate that makes it one of the most fatal human malignancies. Unfortunately, despite the serious improvement in the survival of most cancers, there has been a minor advance in pancreatic cancer (PC). Major advances in PC treatment have been assessed over the bygone twenty-year time span, yet some complications make the survival of the patients shorter. Getting to know the PC tumor microenvironment (TME) and the immunosuppression that happens during the pathogenesis of this malignancy could be a great help to understand the nature of the immune system and find better treatment modalities based on it. Although many immune cells are present in PC, immunosuppression of the TME leads to severe immune dysfunction in the patients, therefore immune effectors fail to do their functions. Lately, immunotherapy has been presented as one of the promising treatment strategies for different malignancies including hepatocellular carcinoma, melanoma, non-small cell lung cancer, and kidney cancer. In PC, there has been shown promising results centered around the TME, immune checkpoint inhibitors, cancer vaccines, and other approaches especially when used as combinational therapy. Here we dig a little deeper into the role of the immune system and possible therapeutic options in the treatment of PC.

Javadrashid D ，Baghbanzadeh A ，Hemmat N ，Hajiasgharzadeh K ，Nourbakhsh NS ，Lotfi Z ，Baradaran B ... -  《-》

The reciprocal regulation between host tissue and immune cells in pancreatic ductal adenocarcinoma: new insights and therapeutic implications.

Liu X ，Xu J ，Zhang B ，Liu J ，Liang C ，Meng Q ，Hua J ，Yu X ，Shi S ... -  《Molecular Cancer》

T-cell programming in pancreatic adenocarcinoma: a review.

Seo YD ，Pillarisetty VG 《-》

The critical roles of activated stellate cells-mediated paracrine signaling, metabolism and onco-immunology in pancreatic ductal adenocarcinoma.

Fu Y ，Liu S ，Zeng S ，Shen H ... -  《Molecular Cancer》

Stroma Involvement in Pancreatic Ductal Adenocarcinoma: An Overview Focusing on Extracellular Matrix Proteins.

Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide and is predicted to become second in 2030 in industrialized countries if no therapeutic progress is made. Among the different types of pancreatic cancers, Pancreatic Ductal Adenocarcinoma (PDAC) is by far the most represented one with an occurrence of more than 90%. This specific cancer is a devastating malignancy with an extremely poor prognosis, as shown by the 5-years survival rate of 2-9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients. Pancreatic tumors progress with few specific symptoms and are thus at an advanced stage at diagnosis in most patients. This malignancy is characterized by an extremely dense stroma deposition around lesions, accompanied by tissue hypovascularization and a profound immune suppression. Altogether, these combined features make access to cancer cells almost impossible for conventional chemotherapeutics and new immunotherapeutic agents, thus contributing to the fatal outcomes of the disease. Initially ignored, the Tumor MicroEnvironment (TME) is now the subject of intensive research related to PDAC treatment and could contain new therapeutic targets. In this review, we will summarize the current state of knowledge in the field by focusing on TME composition to understand how this specific compartment could influence tumor progression and resistance to therapies. Attention will be paid to Tenascin-C, a matrix glycoprotein commonly upregulated during cancer that participates to PDAC progression and thus contributes to poor prognosis.

Liot S ，Balas J ，Aubert A ，Prigent L ，Mercier-Gouy P ，Verrier B ，Bertolino P ，Hennino A ，Valcourt U ，Lambert E ... -  《Frontiers in Immunology》