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Scientists of the University Medical Center Göttingen (UMG) have identified new interactions between pancreatic cancer cells and the immune system. The insights of the research group provide important approaches for innovative therapies. The findigs are published in the renowned scientific journal „Nature Communications”.
Pancreatic cancer remains one of the most aggressive and deadly cancer types to date. It is particularly difficult to due to the significant variability often found within a single patient’s tumor. This variability, known as heterogeneity, complicates both the selection and effectiveness of therapies. Especially two tumor subtypes – the classical (CLA) and the basal-like (BL) subtype – play a crucial role in disease progression. When both subtypes are present in one tumor, patient survival rates decline, and the treatment becomes even more challenging.
Scientists of the Max-Eder Junior Research Group, led by Dr. Shiv K. Singh in the Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology in the University Medical Center Göttingen (UMG), have now investigated the mechanisms that influence these subtypes in a new study, and researched their interactions with the immune system. They discovered that macrophages play an essential role in these processes. Macrophages are immune cells, that are attracted to the tumor by signal proteins. When macrophages and tumor cells work together, they create an environment that suppresses the activity of cytotoxic T cells, the “killer cells” of the immune system. This further weakens the immune defense.
The findings of the research group from Göttingen open up a promising approach for new treatment strategies for pancreatic cancer. By specifically targeting immune cells and inflammatory signaling pathways, patients who have previously responded poorly to existing therapies could benefit from new therapy combinations in the future. The results are published in the renowned scientific journal “Nature Communications”.
Original publication:
Lukas Klein, Mengyu Tu, Niklas Krebs, Laura Urbach, Daniela Grimm, Muhammad Umair Latif, Frederike Penz, Anna Blandau, Xueyan Wu, Rebecca Diya Samuel, Stefan Küffer, Florian Wegwitz, Nathan Chan, Kazeera Aliar, Foram Vyas, Uday Kishore, Elisabeth Hessmann, Andreas Trumpp, Elisa Espinet, Argyris Papantonis, Rama Khokha, Volker Ellenrieder, Barbara Grünwald and Shiv K. Singh. Spatial tumor immune heterogeneity facilitates subtype co-existence and therapy response in pancreatic cancer. Nature Communications (2025). DOI: 10.1038/s41467-024-55330-7
About the study
The researchers demonstrated that pancreatic cancer tumors often consist of a mix of CLA and BL subtypes, which respond differently to treatments. This heterogeneity complicates the development of targeted therapeutic approaches. The study revealed that one of the subtypes specifically suppresses the immune system’s defense mechanisms to enhance its “survival” in the body. This manipulation occurs through so-called epigenetic programs, which influences which genes are active. This alteration inhibits the immune defense against the tumor, thereby creating a favorable environment for tumor growth.
„Our investigations show that the interplay between the tumor and immune cells plays a central role”, explains Dr. Shiv K. Singh, head of the research group and senior author of the study. “A key insight for us is that immune cells, such as macrophages, can influence the tumor and make it more aggressive while simultaneously weakening the immune defense.” The study identified the pro-inflammatory signaling protein TNF-α, secreted by macrophages, as a key factor. The researchers demonstrated that tumors exploit TNF-α to control immune defense processes that could otherwise inhibit their growth. The failure of these protective mechanisms leads to faster disease progression and poorer survival outcomes for patients.
New therapeutic approaches
Building on these findings, the researchers aim to develop a novel combination therapy. This approach integrates immunotherapy with conventional chemotherapy to specifically inhibit pro-inflammatory macrophages while restoring the function of cytotoxic T cells. Initial preclinical tests in animal models show promising results: harmful inflammatory reactions in the tumor were reduced, and survival rates improved.
“Our results provide new insights into the mechanisms by which tumors evade the immune defense,” says Dr. Singh. “With this knowledge, we aim to strategically alter the tumor environment to strengthen the immune response.” A particularly promising approach is to inhibit TNF-α-producing macrophages to reduce tumor aggressiveness. Future clinical studies will need to determine if and how these laboratory successes can be translated into medical practice for cancer patients. The goal is to sustainably improve survival rates and the quality of life for those affected.
University Medical Center Göttingen, Georg-August-University
Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology
Dr. Shiv K. Singh
Robert-Koch-Str. 40, 37075 Göttingen
Phone 0551 / 39-64767
shiv.singh@med.uni-goettingen.de
Lukas Klein, Mengyu Tu, Niklas Krebs, Laura Urbach, Daniela Grimm, Muhammad Umair Latif, Frederike Penz, Anna Blandau, Xueyan Wu, Rebecca Diya Samuel, Stefan Küffer, Florian Wegwitz, Nathan Chan, Kazeera Aliar, Foram Vyas, Uday Kishore, Elisabeth Hessmann, Andreas Trumpp, Elisa Espinet, Argyris Papantonis, Rama Khokha, Volker Ellenrieder, Barbara Grünwald and Shiv K. Singh. Spatial tumor immune heterogeneity facilitates subtype co-existence and therapy response in pancreatic cancer. Nature Communications (2025). DOI: 10.1038/s41467-024-55330-7
A look under the microscope: Molecular analyses reveal how cancer cells (red) and immune cells (gree ...
umg
Investigating the link between pancreatic cancer and the immune system: Dr. Lukas Klein and Dr. Shi ...
umg/lukas klein
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