Countering tumor-induced immunosuppression during immunotherapy for pancreatic cancer

Abstract

Background: Vaccines for pancreatic cancer have been challenged by a number of factors, especially the immunosuppressive microenvironment within the tumor that allows for escape from immune surveillance. Objective/methods: We sought to identify results that define mechanisms of pancreatic-cancer-associated immunosuppression and strategies that might be useful to overcome them thereby resulting in effective immune responses to cancer vaccines capable of deleting pancreatic cancer cells. Results/conclusion: Immunosuppressive tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSC), and regulatory T cells (Treg) reside in tumors, and their products along with tumor derived products (such as VEGF, TGFβ and IL-10), create a microenvironment that counters immune activation and attack. Immunotherapy with cancer vaccines must include strategies to modulate these immunosuppressive cell types and tumor byproducts. Clinical trials are beginning to test these strategies.

Keywords::

• clinical trials
• IL-10
• immunosuppression
• microenvironment
• myeloid-derived suppressor cells (MDSC)
• OX40
• regulatory T cells (Tregs)
• TGFβ
• toll-like receptors (TLRs)
• tumor products
• tumor-associated macrophages (TAMs)
• vaccine