Host B7x promotes pulmonary metastasis of breast cancer

Yael M. Abadi, Hyungjun Jeon, Kim C. Ohaegbulam, Lisa Scandiuzzi, Kaya Ghosh, Kimberly A. Hofmeyer, Jun Sik Lee, Anjana Ray, Claudia Gravekamp, Xingxing Zang

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

B7x (B7-H4 or B7S1) is an inhibitorymember of the B7 family of T cell costimulation. It is expressed in low levels in healthy peripheral tissues, such as the lung epithelium, but is overexpressed in a variety of human cancers with negative clinical associations, including metastasis. However, the function of B7x in the context of cancer, whether expressed on cancer cells or on surrounding "host" tissues, has not been elucidated in vivo. We used the 4T1 metastatic breast cancer model and B7x knockout (B7x-/-) mice to investigate the effect of host tissue-expressed B7x on cancer. We found that 4T1 cells were B7x negative in vitro and in vivo, and B7x-/- mice had significantly fewer lung 4T1 tumor nodules than did wild-type mice. Furthermore, B7x-/- mice showed significantly enhanced survival and a memory response to tumor rechallenge. Mechanistic studies revealed that the presence of B7x correlated with reduced general and tumor-specific T cell cytokine responses, as well as with an increased infiltration of immunosuppressive cells, including tumor-associated neutrophils, macrophages, and regulatory T cells, into tumorbearing lungs. Importantly, tumor-associated neutrophils strongly bound B7x protein and inhibited the proliferation of both CD4 and CD8 T cells. These results suggest that host B7x may enable metastasizing cancer cells to escape local antitumor immune responses through interactions with the innate and adaptive immune systems. Thus, targeting the B7x pathway holds much promise for improving the efficacy of immunotherapy for metastatic cancer.

Original languageEnglish (US)
Pages (from-to)3806-3814
Number of pages9
JournalJournal of Immunology
Volume190
Issue number7
DOIs
StatePublished - Apr 1 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Abadi, Y. M., Jeon, H., Ohaegbulam, K. C., Scandiuzzi, L., Ghosh, K., Hofmeyer, K. A., Lee, J. S., Ray, A., Gravekamp, C., & Zang, X. (2013). Host B7x promotes pulmonary metastasis of breast cancer. Journal of Immunology, 190(7), 3806-3814. https://doi.org/10.4049/jimmunol.1202439