Immune checkpoint blockade in human cancer therapy: lung cancer and hematologic malignancies

Immunotherapy. 2016 Jun;8(7):809-19. doi: 10.2217/imt-2016-0001.

Abstract

Tumor immune evasion is one of the hallmarks of cancer, and expression of the B7 family of immune checkpoints (PD-L1, PD-L2, B7-H3, B7x and HHLA2) is one mechanism of immune evasion by tumors to suppress T-cell function. Antibodies blocking these interactions of B7-1/B7-2/CTLA-4 and PD-L1/PD-L2/PD-1 have had remarkable clinical success in several cancers and are less toxic than traditional chemotherapy. Even though only a small proportion of patients respond to checkpoint blockade, the duration of such responders due to immunological memory is remarkable and is longer than would be expected with any other agent in refractory disease. In this article, we review the therapeutic trials of blocking these pathways in human lung cancer and hematological malignancies.

Keywords: CTLA-4; Hodgkin lymphoma; PD-1; PD-L1; immune checkpoint inhibitor; immunotherapy; leukemia; multiple myeloma; non-lymphoma; non-small-cell lung cancer; squamous cell lung cancer.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Costimulatory and Inhibitory T-Cell Receptors / immunology*
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / therapy*
  • Humans
  • Immunologic Memory
  • Lung Neoplasms / immunology
  • Lung Neoplasms / therapy*
  • Treatment Outcome
  • Tumor Escape

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Costimulatory and Inhibitory T-Cell Receptors