Overcoming immunotherapeutic resistance by targeting the cancer inflammation cycle

Semin Cancer Biol. 2020 Oct;65:38-50. doi: 10.1016/j.semcancer.2020.01.002. Epub 2020 Jan 15.

Abstract

Inflammation is a hallmark of cancer and supports tumor growth, proliferation, and metastasis, but also inhibits T cell immunosurveillance and the efficacy of immunotherapy. The biology of cancer inflammation is defined by a cycle of distinct immunological steps that begins during disease conception with the release of inflammatory soluble factors. These factors communicate with host organs to trigger bone marrow mobilization of myeloid cells, trafficking of myeloid cells to the tumor, and differentiation of myeloid cells within the tumor bed. Tumor-infiltrating myeloid cells then orchestrate an immunosuppressive microenvironment and assist in sustaining a vicious cycle of inflammation that co-evolves with tumor cells. This Cancer-Inflammation Cycle acts as a rheostat or "inflammostat" that impinges upon T cell immunosurveillance and prevents the development of productive anti-tumor immunity. Here, we define the major nodes of the Cancer-Inflammation Cycle and describe their impact on T cell immunosurveillance in cancer. Additionally, we discuss emerging pre-clinical and clinical data suggesting that intervening upon the Cancer-Inflammation Cycle will be a necessary step for broadening the potential of immunotherapy in cancer.

Keywords: Cancer; Immunotherapy; Inflammation; Inflammostat; Macrophage; Myeloid cells; T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Movement / drug effects
  • Drug Resistance, Neoplasm / immunology*
  • Humans
  • Immunotherapy / adverse effects
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Inflammation / pathology
  • Myeloid Cells / immunology
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • T-Lymphocytes / immunology*
  • Tumor Microenvironment / immunology