Combination cancer immunotherapies tailored to the tumour microenvironment

Nat Rev Clin Oncol. 2016 Mar;13(3):143-58. doi: 10.1038/nrclinonc.2015.209. Epub 2015 Nov 24.


Evidence suggests that cancer immunotherapy will be a major part of the combination treatment plan for many patients with many cancer types in the near future. There are many types of immune processes involving different antitumour and tumour-promoting leucocytes, and tumour cells use many strategies to evade the immune response. The tumour microenvironment can help determine which immune suppressive pathways become activated to restrain antitumour immunity. This includes immune checkpoint receptors on effector T-cells and myeloid cells, and release of inhibitory cytokines and metabolites. Therapeutic approaches that target these pathways, particularly immune-checkpoint receptors, can induce durable antitumour responses in patients with advanced-stage cancers, including melanoma. Nevertheless, many patients do not have a good response to monotherapy approaches and alternative strategies are required to achieve optimal therapeutic benefit. These strategies include eliminating the bulk of tumour cells to provoke tumour-antigen release and antigen-presenting cell (APC) function, using adjuvants to enhance APC function, and using agents that enhance effector-cell activity. In this Review, we discuss the stratification of the tumour microenvironment according to tumour-infiltrating lymphocytes and PD-L1 expression in the tumour, and how this stratification enables the design of optimal combination cancer therapies tailored to target different tumour microenvironments.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / immunology
  • B7-H1 Antigen / metabolism
  • Humans
  • Immunotherapy / methods*
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Signal Transduction / drug effects
  • Treatment Outcome
  • Tumor Escape / drug effects
  • Tumor Microenvironment / drug effects*


  • Adjuvants, Immunologic
  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • CD274 protein, human