Increase in frequency of myeloid-derived suppressor cells in mice with spontaneous pancreatic carcinoma
Fei Zhao1, Sonja Obermann, Reinhard von Wasielewski
1Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.
Abstract:
Pancreatic adenocarcinoma is one of the deadliest cancers with poor survival and limited treatment options. Immunotherapy is an attractive option for this cancer that needs to be further developed. Tumours have evolved a variety of mechanisms to suppress host immune responses. Understanding these responses is central in developing immunotherapy protocols. The aim of this study was to investigate potential immune suppressor mechanisms that might occur during development of pancreatic tumours. Myeloid-derived suppressor cells (MDSC) from mice with spontaneous pancreatic tumours, mice with premalignant lesions as well as wild-type mice were analysed. An increase in the frequency of MDSC early in tumour development was detected in lymph nodes, blood and pancreas of mice with premalignant lesions and increased further upon tumour progression. The MDSC from mice with pancreatic tumours have arginase activity and suppress T-cell responses, which represent the hallmark functions of these cells. Our study suggests that immune suppressor mechanisms generated by tumours exist as early as premalignant lesions and increase with tumour progression. These results highlight the importance of blocking these suppressor mechanisms early in the disease in developing immunotherapy protocols.
Insights
Immune suppressor cells called myeloid-derived suppressor cells (MDSC) increase early in pancreatic cancer development and suppress immune responses. Blocking these cells early may improve immunotherapy for pancreatic adenocarcinoma.
Area of Science:
- Oncology
- Immunology
Background:
- Pancreatic adenocarcinoma has poor survival rates and limited treatment options.
- Tumors employ immune suppression mechanisms, hindering effective immunotherapy.
- Understanding these mechanisms is crucial for developing pancreatic cancer treatments.
Purpose of the Study:
- To investigate immune suppressor mechanisms during pancreatic tumor development.
- To analyze myeloid-derived suppressor cells (MDSC) in mice with varying stages of pancreatic lesions.
- To understand the role of MDSC in immune suppression in pancreatic cancer.
Main Methods:
- Analysis of myeloid-derived suppressor cells (MDSC) frequency and function.
- Comparison of MDSC in mice with spontaneous pancreatic tumors, premalignant lesions, and wild-type controls.
- Assessment of MDSC arginase activity and T-cell suppression in tumor-bearing mice.
Main Results:
- Increased frequency of MDSC detected early in premalignant lesions and progressing tumors.
- MDSC frequency elevated in lymph nodes, blood, and pancreas.
- MDSC from pancreatic tumors exhibited arginase activity and suppressed T-cell responses.
Conclusions:
- Immune suppression via MDSC occurs early in pancreatic tumor development.
- MDSC accumulation and function increase with tumor progression.
- Targeting MDSC early may enhance immunotherapy efficacy for pancreatic adenocarcinoma.
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