Targeting tumor-associated macrophages to combat pancreatic cancer
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Ran Cui1,2, Wen Yue3, Edmund C. Lattime3, Mark N. Stein3, Qing Xu1 and Xiang-Lin Tan3,4
1 Department of Oncology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai, P. R. China
2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
3 Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
4 Department of Epidemiology, School of Public Health, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
Xiang-Lin Tan, email:
Keywords: tumor-associated macrophages, tumor microenvironment, pancreatic cancer, chemoprevention
Received: January 13, 2016 Accepted: May 05, 2016 Published: May 15, 2016
The tumor microenvironment is replete with cells that evolve with and provide support to tumor cells during the transition to malignancy. The hijacking of the immune system in the pancreatic tumor microenvironment is suggested to contribute to the failure to date to produce significant improvements in pancreatic cancer survival by various chemotherapeutics. Regulatory T cells, myeloid derived suppressor cells, and fibroblasts, all of which constitute a complex ecology microenvironment, can suppress CD8+ T cells and NK cells, thus inhibiting effector immune responses. Tumor-associated macrophages (TAM) are versatile immune cells that can express different functional programs in response to stimuli in tumor microenvironment at different stages of pancreatic cancer development. TAM have been implicated in suppression of anti-tumorigenic immune responses, promotion of cancer cell proliferation, stimulation of tumor angiogenesis and extracellular matrix breakdown, and subsequent enhancement of tumor invasion and metastasis. Many emerging agents that have demonstrated efficacy in combating other types of tumors via modulation of macrophages in tumor microenvironments are, however, only marginally studied for pancreatic cancer prevention and treatment. A better understanding of the paradoxical roles of TAM in pancreatic cancer may pave the way to novel preventive and therapeutic approaches. Here we give an overview of the recruitment and differentiation of macrophages, TAM and pancreatic cancer progression and prognosis, as well as the potential preventive and therapeutic targets that interact with TAM for pancreatic cancer prevention and treatment.
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