Advances in Immunosuppressive Microenvironment Remodeling and Targeted Drug Intervention in Pancreatic Cancer

Pancreatic cancer remains one of the deadliest threats to human life, and there is an urgent need for effective treatment strategies. The tumor microenvironment (TME) comprising abnormal tumor blood vessels, extracellular matrix components, endothelial cells, pericytes, tumor-associated fibroblasts, smooth muscle cells, and immune cells, plays a crucial role in the occurrence, growth, and metastasis of tumors. The immunosuppressive nature of the TME significantly contributes to the failure of various anti-tumor treatments, including immunotherapy. Clinical evidence for therapies targeting the tumor immune microenvironment in pancreatic cancer is limited compared to treatments involving anti-PD-1/PD-L1 or CTLA-4 antibodies. Addressing the complexity and heterogeneity of the tumor immune microenvironment through research at the single-cell and molecular levels can provide practical and precise solutions for diverse patient populations and cancer types, which is promising for enhancing the therapeutic efficacy targeting the tumor immune microenvironments. In recent years, many studies have increasingly focused on improving therapeutic efficacy by targeting and reshaping TME.

This topic aims to elaborate on the latest strategies and studies for targeting and reshaping the tumor microenvironment (TME) of pancreatic cancer, providing innovative approaches for pancreatic cancer treatment. Key strategies include improving tumor hypoxia, targeting tumor blood vessels, targeting tumor-associated fibroblasts, extracellular matrix components, tumor-associated macrophages, dendritic cells, and so on. These approaches aim to enhance the infiltration of drugs and endogenous anti-tumor immune cells by weakening the matrix barrier or improving the immunosuppressive microenvironment, thereby enhancing the effectiveness of anti-tumor therapy. Existing issues and exploration of future developments in this field are both highly welcome in this topic.

Specifically, researchers are welcome to address, but not limited to, the following sub-topics.
● Small molecule drugs targeting oncogenic pathways in tumor cells and tumor microenvironment of pancreatic cancer
● The latest technology for developing small molecules that directly stimulate anti-tumor immune responses in pancreatic cancer
● Establishment and treatment strategy of targeted drugs for pancreatic cancer based on cross-presentation
● Drug development targeting KRAS to drive immune remodeling of tumor microenvironment of pancreatic cancer
● Drug delivery system targeting the tumor stromal microenvironment of pancreatic cancer
● Targeting the tumor microenvironment to regulate tumor cell metabolism and enhance anti-pancreatic cancer immunotherapy strategies
● New immunotherapy targets for reshaping the tumor microenvironment of pancreatic cancer
● Immune combination therapy reprogramming tumor immune microenvironment for pancreatic cancer treatment
● Application of artificial intelligence in biomarkers and target drug development of pancreatic cancer

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.

Keywords: pancreatic cancer, immunotherapy, molecular targets, tumour microenvironment, targeted drug

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