The Emerging Role of Immunosurveillance in Dictating Metastatic Spread in Breast Cancer

Abstract

It is now well known that the immune system can recognize transformed cells and control the initiation and growth of some cancers, a process termed tumor immunosurveillance. Key regulators of this process have been described in the primary tumor setting, where the balance of protumor and antitumor responses dictates tumor initiation and progression. Accumulating evidence suggests that immunosurveillance may also be critical for regulating metastatic spread, the most fatal aspect of cancer, and that mechanisms of overcoming immune control may be quite different from those at the primary site. Our recent findings support loss of type I interferon (IFN) signaling as a tumor-cell intrinsic mechanism of evading metastasis-specific immune responses in breast cancer. We revealed that type I IFN-induced innate (natural killer) and adaptive (CD8 þ T cell) responses suppressed bone metastatic growth and this was associated with decreased accumulation of immune suppressor cells (myeloid-derived suppressor cells). This review summarizes recent findings that are in support of tumorinduced immunosurveillance in regulating metastatic spread, including evidence that immune regulation of primary tumors may be distinct from those dictating metastasis. Cancer Res; 73(19); 5852-7. Ó2013 AACR.

Bioinformatic analysis reveals a pattern of STAT3-associated gene expression specific to basal-like breast cancers in human tumors

“…With the increasing number of therapeutic molecules specifically targeted toward STAT3 coming through clinical trials (23)(24)(25), the inclusion of these compounds in subtype-specific breast cancer treatment may be a promising avenue. This analysis yields a farreaching protein interaction network and potential associations with inflammation and aberrant immunological cell recruitment, a common problem associated with many basal-like cancers and a prognostic factor when assessing patient survival (17).…”

“…In both groups the highestscoring ontologies are those associated with immunological signaling and innate immune response. Basal-like cancers are known for their aberrant immunological signaling and associated proinflammatory conditions (17). Not only does STAT3 signaling differentially affect a wide array of genes in basal-like cancers but many of these genes are specifically known to be cancer-associated factors.…”

Epithelial-mesenchymal transition leads to NK cell–mediated metastasis-specific immunosurveillance in lung cancer

“…It is now increasingly clear that the microenvironment and the conditions tumor cells encounter in the primary tumor are disparate from what they encounter during metastasis. This suggests that mechanisms of immunosurveillance in the primary tumor may also be different from those that regulate metastatic spread (3), indicating the existence of metastasis-specific immunosurveillance (3)(4)(5)(6)(7)(8).…”

Loss of Host Type-I IFN Signaling Accelerates Metastasis and Impairs NK-cell Antitumor Function in Multiple Models of Breast Cancer

“…Tumor cells can use multiple immune-evasive tactics to survive at various metastatic sites (6), including our recent findings that show a requirement for breast tumor cells to suppress their innate type-I IFN pathway to colonize the bone (7). The type-I IFN family was originally characterized as a group of soluble factors produced by almost all cells in the body that were able to confer an antiviral state (8,9).…”