The tumor-associated stroma has been shown to play a significant role in cancer formation. Paracrine signaling interactions between epithelial tumor cells and stromal cells are a key component in the transformation and proliferation of tumors in several organs. Whereas the intracellular signaling pathways regulating the expression of several pro- and antiangiogenic proteins have been well characterized in human cancer cells, the intercellular signaling that takes place between tumor cells and the surrounding tumor-associated stroma has not been as extensively studied with regard to the regulation of angiogenesis. In this chapter we define the key players in the regulation of angiogenesis and examine how their expression is regulated in the tumor-associated stroma. The resulting analysis is often seemingly paradoxical, underscoring the complexity of intercellular signaling within tumors and the need to better understand the environmental context underlying these signaling mechanisms.
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http://dx.doi.org/10.1101/cshperspect.a006676 | DOI Listing |
J Immunother Cancer
December 2024
Pritzker School of Molecular Engineering, The University of Chicago, Chicago, Illinois, USA
Background: The use of immune checkpoint inhibitors (CPIs) has become a dominant regimen in modern cancer therapy, however immune resistance induced by tumor-associated macrophages (TAMs) with immune suppressive and evasion properties limits responses. Therefore, the rational design of immune modulators that can control the immune suppressive properties of TAMs and polarize them, as well as dendritic cells (DCs), toward a more proinflammatory phenotype is a principal objective in cancer immunotherapy.
Methods: Here, using a protein engineering approach to enhance cytokine residence in the tumor microenvironment, we examined combined stimulation of the myeloid compartment via tumor stroma-binding granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance responses in both DCs and T cells via stroma-binding interleukin-12 (IL-12).
Int J Mol Sci
December 2024
Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University, 66421 Homburg, Germany.
Head and neck squamous cell carcinomas (HNSCC) have an overall poor prognosis, especially in locally advanced and metastatic stages. In most cases, multimodal therapeutic approaches are required and show only limited cure rates with a high risk of tumor recurrence. Anti-PD-1 antibody treatment was recently approved for recurrent and metastatic cases but to date, response rates remain lower than 25%.
View Article and Find Full Text PDFBiomolecules
December 2024
School of Cancer Sciences, Wolfson Wohl Cancer Research Institute, University of Glasgow, Estate, Glasgow G61 1BD, UK.
Colorectal cancer is the third most diagnosed malignancy worldwide and survival outcomes remain poor. Research is focused on the identification of novel prognostic and predictive biomarkers to improve clinical practice. There is robust evidence in the literature that inflammatory cytokine interleukin-6 (IL6) is elevated systemically in CRC patients and that this phenomenon is a predictor of poor survival outcome.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
State Key Laboratory of Systems Medicine for Cancer of Oncology Department and Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Background: To date, a growing body of evidence suggests that unfolded protein response (UPR) sensors play a vital role in carcinogenesis. However, it remains unclear whether they are involved in pancreatic ductal adenocarcinoma (PDAC) and how they relate to clinical outcomes. This study aims to investigate the biological function and mechanism of how a novel UPR sensor, CREB3L1 works in PDAC and further evaluate its clinical application prospect.
View Article and Find Full Text PDFCancer Immunol Immunother
December 2024
Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abundant infiltration of tumor-associated macrophages (TAMs) within the tumor stroma plays a pivotal role in inducing immune escape in pancreatic cancer (PC). Lactate serves as a direct regulator of macrophage polarization and functions, although the precise regulation mechanism remains inadequately understood. Our study revealed that PC cells (PCs) promote macrophage polarization toward M2d through high lactate secretion.
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