Inflammation and Myeloid Cells in Cancer Progression and Metastasis.

Abstract

To date, the most immunotherapy drugs act upon T cell surface proteins to promote tumoricidal T cell activity. However, this approach has to date been unsuccessful in certain solid tumor types including pancreatic, prostate cancer and glioblastoma. Myeloid-related innate immunity can promote tumor progression through direct and indirect effects on T cell activity; improved understanding of this field may provide another therapeutic avenue for patients with these tumors. Myeloid cells can differentiate into both pro-inflammatory and anti-inflammatory mature form depending upon the microenvironment. Most cancer type exhibit oncogenic activating point mutations (ex. P53 and KRAS) that trigger cytokines production. In addition, tumor environment (ex. Collagen, Hypoxia, and adenosine) also regulated inflammatory signaling cascade. Both the intrinsic and extrinsic factor driving the tumor immune microenvironment and regulating the differentiation and function of myeloid cells, T cells activity and tumor progression. In this review, we will discuss the relationship between cancer cells and myeloid cells-mediated tumor immune microenvironment to promote cancer progression and immunotherapeutic resistance. Furthermore, we will describe how cytokines and chemokines produced by cancer cells influence myeloid cells within immunosuppressive environment. Finally, we will comment on the development of immunotherapeutic strategies with respect to myeloid-related innate immunity.