AUTHOR=Agostini Antonio , Orlacchio Arturo , Carbone Carmine , Guerriero Ilaria 

TITLE=Understanding Tricky Cellular and Molecular Interactions in Pancreatic Tumor Microenvironment: New Food for Thought

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.876291

DOI=10.3389/fimmu.2022.876291

ISSN=1664-3224

ABSTRACT=Pancreatic ductal adenocarcinoma (PDAC) represents 90% of all pancreatic cancer cases and shows high mortality rate among all solid tumors. PDAC is often associated to poor prognosis, due to metastasis development and limited efficacy of available treatments. The tumor microenvironment (TME) represents a reliable source of novel targets for therapy, but most of the biological interactions among stromal, immune and cancer cells that populate the TME are still unknown. The great limitation in the efficacy of current treatments is due to the fibrotic TME surrounding cancer cells that physically inhibits the accessibility of anti-cancer drugs, but also to the immunological evolution from a tumor-suppressor to an immunosuppressive environment, during PDAC progression. It is commonly recognized that combinatorial therapies can be the best approach, but a deep understanding of the pathological mechanisms driving tumor progression and immune escape is absolutely needed, to find more effective targets. This review aims to summarize the present knowledge about cellular interactions in the TME, with much attention on immunosuppressive functioning and a specific focus on extracellular matrix (ECM) contribution.