The future of cancer immunotherapy: microenvironment-targeting combinations

Cell Res. 2020 Jun;30(6):507-519. doi: 10.1038/s41422-020-0337-2. Epub 2020 May 28.


Immunotherapy holds the potential to induce durable responses, but only a minority of patients currently respond. The etiologies of primary and secondary resistance to immunotherapy are multifaceted, deriving not only from tumor intrinsic factors, but also from the complex interplay between cancer and its microenvironment. In addressing frontiers in clinical immunotherapy, we describe two categories of approaches to the design of novel drugs and combination therapies: the first involves direct modification of the tumor, while the second indirectly enhances immunogenicity through alteration of the microenvironment. By systematically addressing the factors that mediate resistance, we are able to identify mechanistically-driven novel approaches to improve immunotherapy outcomes.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Drug Resistance, Neoplasm
  • Humans
  • Immunologic Factors / therapeutic use
  • Immunotherapy*
  • Molecular Targeted Therapy
  • Neoplasms / therapy*
  • Tumor Microenvironment / drug effects*


  • Antineoplastic Agents
  • Immunologic Factors