Year: 2020
Type: review
Abstract: Like many tumor types, pancreatic ductal adenocarcinoma (PDAC) exhibits a rich network of tumor-derived cytokines and chemokines that drive recruitment of myeloid cells to the tumor microenvironment (TME). These cells, which include tumor-associated macrophages and myeloid derived suppressor cells, block the recruitment and priming of T cells, resulting in T cell exclusion within the TME. Genetic or pharmacologic disruption of this chemokine/cytokine network reliably converts the PDAC TME to a T cell-high phenotype and sensitizes tumors to immunotherapy across multiple preclinical models. Thus, neutralization of tumor-derived chemokines/cytokines or blockade of their respective receptors represents a potentially potent strategy to reverse myeloid immunosuppression in PDAC, enabling benefit from checkpoint inhibition not otherwise achievable in this disease. Inhibition of oncogenic pathways that drive tumor-intrinsic expression of chemoattractants may be similarly effective.
Source: Frontiers in Immunology
Authors: Robert H. Vonderheide, Adham S. Bear
Institutions: Abramson Cancer Center, University of Pennsylvania
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
OpenAlex ID: W3102932851