T cell coinhibition and immunotherapy in human breast cancer.

Murali Janakiram, Yael M. Abadi, Joseph A. Sparano, Xingxing Zang

Research output: Contribution to journalReview article

28 Scopus citations

Abstract

Costimulation and coinhibition generated by the B7 family and their receptor CD28 family have key roles in regulating T lymphocyte activation and tolerance. These pathways are very attractive therapeutic targets for human cancers including breast cancer. Gene polymorphisms of B7x (B7-H4/B7S1), PD-1 (CD279), and CTLA-4 (CD152) are associated with increased risk of developing breast cancer although the underlying mechanisms are unclear. In human breast cancer microenvironment, up-regulation of coinhibitory B7/CD28 members B7x, B7-H3 (CD276), and PD-L1 (B7-H1/CD274) on tumor cells as well as PD-1 and PD-L1 on tumor-infiltrating immune cells are emerging as immune evasion pathways. Chemotherapy can affect the expression of these molecules, and therefore may dampen the immune response against breast cancer. Immunotherapy targeting T cell coinhibition as monotherapy or combined with standard therapies are in early stages of clinical development, but hold great promise for treatment of human breast cancer.

Original languageEnglish (US)
Pages (from-to)229-236
Number of pages8
JournalDiscovery Medicine
Volume14
Issue number77
StatePublished - Oct 2012
Externally publishedYes

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    Janakiram, M., Abadi, Y. M., Sparano, J. A., & Zang, X. (2012). T cell coinhibition and immunotherapy in human breast cancer. Discovery Medicine, 14(77), 229-236.