The Role of Myeloid-Derived Suppressor Cells in the Treatment of Pancreatic Cancer

Abstract

Pancreatic cancer has the highest mortality rate of all major cancers, with a 5-year survival rate of about 10%. Early warning signs and symptoms of pancreatic cancer are vague or nonexistent, and most patients are diagnosed in Stage IV, when surgery is not an option for about 80%–85% of patients. For patients with inoperable pancreatic cancer, current conventional treatment modalities such as chemotherapy and radiotherapy (RT) have suboptimal efficacy. Tumor progression is closely associated with the tumor microenvironment, which includes peripheral blood vessels, bone marrow-derived inflammatory cells, fibroblasts, immune cells, signaling molecules, and extracellular matrix. Tumor cells affect the microenvironment by releasing extracellular signaling molecules, inducing peripheral immune tolerance, and promoting tumor angiogenesis. In turn, the immune cells of the tumor affect the survival and proliferation of cancer cells. Myeloid-derived suppressor cells are key cellular components in the tumor microenvironment and exert immunosuppressive functions by producing cytokines, recognizing other immune cells, and promoting tumor growth and metastasis. Myeloid-derived suppressor cells are the main regulator of the tumor immune response and a key target for tumor treatments. Since the combination of RT and immunotherapy is the main strategy for the treatment of pancreatic cancer, it is very important to understand the immune mechanisms which lead to MDSCs generation and the failure of current therapies in order to develop new target-based therapies. This review summarizes the research advances on the role of Myeloid-derived suppressor cells in the progression of pancreatic cancer and its treatment application in recent years.

Current Status and Perspectives of Pancreatic Cancer Tumor Microenvironment and Therapy

“…MDSCs can crosstalk with diverse immune cells. MDSCs affect macrophage and neutrophil polarisation and activation, interfere with macrophage and dendritic cell antigen-presenting functions, and inhibit NK cell cytocidal action [31]. All MDSC subpopulations are immunosuppressive, but the mechanism of suppression varies among subpopulations.…”

Breaking Down Barriers in Drug Delivery by Stromal Remodeling Approaches in Pancreatic Cancer

“…Immune cells, including tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs), contribute significantly to the immunosuppressive microenvironment in pancreatic cancer . TAMs predominantly adopt a tumor-promoting M2 phenotype, secreting immunosuppressive cytokines such as interleukin-10 (IL-10) and TGF-β to facilitate tumor progression. , MDSCs exert immunosuppressive effects by inhibiting natural killer cell function and CD4 + /CD8 + T cell activity, while Tregs suppress antitumor immune responses through interleukin-2 consumption and effector T cell inhibition. − …”

Potential Medical Use of Fullerenols After Two Decades of Oncology Research

“…21 Not only is it still in use, but many reviews and original scientific papers are still being published on its usability, safety, different formulation improvements, and targeted therapies. Initially, DOX was confirmed to be effective for a few types of tumors only, although it is now used in many treatments to stop the growth of cancer cells in bones, 93,94 liver, 97,102 prostate, 99,101 cervical tissue, 100 breasts, 87,89,95,96,98,108 pancreas, 86,103 lung, 99,104 ovarium, 105 colon, 106,107 and the brain. 92 Considering all the scientific evidence presented in this section, future research should focus on formulation improvement and the safety profile of the FRLs used as antioxidants to protect organs from toxicity in DOX-related treatments.…”

“… 21 Not only is it still in use, but many reviews and original scientific papers are still being published on its usability, safety, different formulation improvements, and targeted therapies. 86 - 108 Initially, DOX was confirmed to be effective for a few types of tumors only, although it is now used in many treatments to stop the growth of cancer cells in bones, 93 , 94 liver, 97 , 102 prostate, 99 , 101 cervical tissue, 100 breasts, 87 , 89 , 95 , 96 , 98 , 108 pancreas, 86 , 103 lung, 99 , 104 ovarium, 105 colon, 106 , 107 and the brain. 92 …”