Combinatorial Cancer Immunotherapies

Adv Immunol. 2016;130:251-77. doi: 10.1016/ Epub 2016 Jan 12.


T cell checkpoint blockade therapies are revolutionizing the treatment of patients with cancer. Highlighted by the recent success of PD-1 plus CTLA-4 blockade in patients with melanomas, synergistic immunotherapy combinations of modalities represent an important opportunity to improve responses and outcomes for patients. We review the rationale and experience with T cell checkpoint blockade in combination with targeting of other coinhibitory or costimulatory checkpoints, immunomodulatory molecules in the tumor microenvironment, and other anticancer modalities such as vaccines, chemotherapy, and radiation.

Keywords: 4-1BB/CD137; CTLA-4; Chemotherapy; Combination immunotherapy; GITR; IDO; IL-2; LAG-3; OX-40; Oncolytic virus; PD-1; PD-L1; Radiation; T cell checkpoint blockade; TIM-3.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Cell Cycle Checkpoints / immunology*
  • Combined Modality Therapy
  • Costimulatory and Inhibitory T-Cell Receptors / agonists
  • Costimulatory and Inhibitory T-Cell Receptors / antagonists & inhibitors
  • Costimulatory and Inhibitory T-Cell Receptors / therapeutic use*
  • Humans
  • Immunotherapy*
  • Mice
  • Molecular Targeted Therapy
  • Neoplasms / therapy*
  • Oncolytic Viruses / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / physiology
  • Tumor Microenvironment / immunology*


  • Antineoplastic Agents
  • Costimulatory and Inhibitory T-Cell Receptors