Targeting the Tumor Microenvironment of Leukemia and Lymphoma

Trends Cancer. 2019 Jun;5(6):351-364. doi: 10.1016/j.trecan.2019.05.001. Epub 2019 Jun 5.

Abstract

Despite progress in exploiting therapeutically the genetic vulnerabilities of leukemia and lymphoma, the outcome is often extended progression-free survival but not tumor eradication. Lymphomagenesis is not a tumor-autonomous process, and the onset and progression of tumors requires reciprocal crosstalk with the tumor microenvironment (TME). Minimal residual disease and immunosurveillance are also regulated by factors in the TME. Here, we dissect the stromal compartment in lymphoid organs, focusing on conditions that are prevalent in an autochthonous environment for lymphoid neoplasia. Identification of tumor-promoting factors is instrumental in the selection of therapeutic targets that are part of the immune system. Targeting the TME is an appealing treatment option for lymphoma because this compartment is subject to low selective pressure for mutations.

Keywords: adoptive T cell therapy; effector immune cell exhaustion; immune escape; myeloid-derived suppressor cells; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cancer-Associated Fibroblasts / immunology
  • Cancer-Associated Fibroblasts / metabolism
  • Humans
  • Immunomodulation
  • Immunotherapy
  • Immunotherapy, Adoptive
  • Leukemia / immunology*
  • Leukemia / pathology*
  • Leukemia / therapy
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Lymphoma / immunology*
  • Lymphoma / pathology*
  • Lymphoma / therapy
  • Molecular Targeted Therapy
  • Myeloid-Derived Suppressor Cells / immunology
  • Myeloid-Derived Suppressor Cells / metabolism
  • Myeloid-Derived Suppressor Cells / pathology
  • Tumor Escape
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology*