Interfering with coinhibitory molecules: BTLA/HVEM as new targets to enhance anti-tumor immunity

Immunol Lett. 2013 Mar;151(1-2):71-5. doi: 10.1016/j.imlet.2013.01.008. Epub 2013 Feb 21.


Despite the powerful aspects of immune reactions, most often tumor cells are able to evade immune recognition and destruction. Cosignaling molecules from the B7/CD28 and TNF/TNFR superfamilies emerge as novel targets in immunotherapy. Upregulation of coinhibitory molecules by the tumor cells or tumor-infiltrating lymphocytes clearly attenuates T-cell responses against cancer and appears to be a mechanism exerted by the tumor to escape immune response. Today, a variety of coinhibitory molecules, including CTLA-4 and PD1 have been implicated in immune escape of cancer cells. Antagonist antibodies are developed to overcome immune evasion and until now anti-CTLA-4 and anti-PD1 antibodies have been tested in clinical trials with encouraging results. Here we summarize the recent advances made on PD1/PD1 ligands expression in cancer and we discuss about another couple of inhibitory molecules, BTLA and its ligand HVEM and their potential role in immune escape. Such information may provide novel therapeutic targets to reverse tumor-induced T-cell dysfunction in patients with advanced cancers.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / metabolism*
  • Neoplasms / therapy
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism
  • Receptors, Immunologic / metabolism*
  • Receptors, Tumor Necrosis Factor, Member 14 / metabolism*
  • Tumor Escape / genetics
  • Tumor Escape / immunology


  • BTLA protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Immunologic
  • Receptors, Tumor Necrosis Factor, Member 14