Commensal bacteria are crucial to maintain immune homeostasis in mucosal tissues and disturbances in their ecology can affect disease susceptibility. Here, we report evidence that commensal bacteria shape the efficiency of immune surveillance in mucosal tissues. Antibiotic-treated (Abt) mice were more susceptible to development of engrafted B16/F10 melanoma and Lewis lung carcinoma, exhibiting a shortened mean survival time with more numerous and larger tumor foci in the lungs. The defective antitumor response of Abt mice was independent of dehydration caused by antibiotics. Host defenses relied upon intact commensal bacteria with no class specificity. Mechanistic investigations revealed a defective induction of the γδT17 cell response in lungs of Abt mice; here, more aggressive tumor development was observed, possibly related to a reduction in IL6 and IL23 expression there. Adding normal γδT cells or supplementing IL17 restored the impaired immune surveillance phenotype in Abt mice. Overall, our results demonstrated the importance of commensal bacteria in supporting the host immune response against cancer, defined an important role for γδT17 responses in the mechanism, and suggested deleterious effects of antibiotic treatment on cancer susceptibility and progression. Cancer Res; 74(15); 1–12. ©2014 AACR.

Biological responses to estrogens in normal and malignant tissues are mainly mediated by the estrogen receptors ERα and ERβ, which function as ligand-activated transcription factors. In addition, the G protein–coupled receptor GPR30 (GPER) mediates estrogenic signaling in breast cancer cells and cancer-associated fibroblasts (CAF) that contribute to cancer progression. In this study, we evaluated the role elicited by GPER in the estrogen-regulated expression and function of vascular endothelial growth factor (VEGF) in ER-negative breast cancer cells and CAF. We demonstrated that 17β-estradiol (E2) and the GPER-selective ligand G-1 triggered a GPER/EGFR/ERK/c-fos signaling pathway that leads to increased VEGF via upregulation of HIF1α. In further extending the mechanisms involved in E2-supported angiogenesis, we also showed that conditioned medium from CAF treated with E2 and G-1 promoted human endothelial tube formation in a GPER-dependent manner. In vivo, ligand-activated GPER was sufficient to enhance tumor growth and the expression of HIF1α, VEGF, and the endothelial marker CD34 in a mouse xenograft model of breast cancer. Our findings offer important new insights into the ability of estrogenic GPER signaling to trigger HIF1α-dependent VEGF expression that supports angiogenesis and progression in breast cancer. Cancer Res; 74(15); 1–12. ©2014 AACR.

Early this summer, oncologists from around the world gathered to hear cutting-edge scientific presentations showcasing new findings in oncology at the American Society of Clinical Oncology. Investigators from Penn Medicine’s Basser Research Center for BRCA presented on a range of topics related to hereditary breast and ovarian cancer. Multiplex TestingKatherine L. Nathanson, MD, presented on ‘multiplex testing” for hereditary cancer risk. Historically, individuals with family histories of cancer were told about the individual genes that may be at the root the family’s history of cancer.For example, a 40-year-old woman with breast cancer whose paternal grandmother also had the disease might be advised to consider BRCA1 and BRCA2 testing. Similarly, a 25-year-old woman with breast cancer might be offered testing for BRCA1 and BRCA2 but also a gene called TP53 associated with much younger breast cancers.Now, in 2014, multiplex or “panel” testing allows a healthcare provider to offer individuals testing for genes which have a predisposition to cancer all at once. This commercially available test has brought opportunities and challenges to the world of cancer genetics for patients and providers alike. ASCO 2014 highlighted the divergent opinions on the new technology.To learn more:Watch Kate Nathanson, MD, discuss her gene panel abstract in an interview with MedPageToday.Read coverage in an article on HemOnc TodayListen to Basser staff Susan Domchek, MD, Kara Maxwell, MD, PhD, and Katherine Nathanson, MD, on WHYY RadioBreast Cancer Worry in TeensFamilies with BRCA mutations or unrelated histories of breast cancer often wonder how this history can impact their girls as they grow into young adults.Basser Investigator, Angela Bradbury, MD, has devoted her career to studying these issues and discusses her abstract on worry and behavior among teens at higher risk for breast cancer.To learn more:Angela Bradbury, MD, speaks with WHYY Radio Read the Penn Medicine press releaseAngela Bradbury, MD, comments on incidental findings from genetic testing hereSide Effects of Risk-Reducing Salpingo OophorectomyFor women who carry BRCA mutations, in is standard practice to discuss preventative removal of the ovaries and fallopian tubes between ages 35 to 40 or after child-bearing is complete.These discussions inevitably lead to concerns about the potential impact of the procedure, which is called risk-reducing salpingo oophorectomy.To learn more about Susan Domchek MD’s research, you can read her interview with MedPage Today or see the Penn Medicine News Release.For hereditary breast and ovarian cancer information, support, and research opportunities, visit Basser.org

More than 700 individuals facing hereditary breast and ovarian cancer gathered at the Philadelphia Marriott for the 2014 Joining FORCEs Conference held by Facing Our Risk of Cancer Empowered in partnership with Penn Medicine’s Basser Research Center for BRCA.As the Philadelphia Inquirer reports, performer Eva Moon spoke at the 2014 joining FORCEs Conference last month, integrating humor with the otherwise serious topic of hereditary cancer.Hereditary breast and ovarian cancer is often caused by mutations in the BRCA1 and BRCA2 genes, which increase risk for breast, ovarian and other cancers.Moon, who carries a BRCA1 mutation, uses humor as a method to cope with tough times. She performs a one-woman musical about her journey with hereditary breast and ovarian cancer.At the conference, Moon shared her personal story, tips for finding humor in daily life, and engaged the audience with a number of songs and activities.”I cried rivers of tears,” she said. But she fought back and underwent a series of major preventative surgeries. Post-recovery, Moon harnesses humor for coping with hard times, and she is teaching others to do the same. “Humor can relieve stress and speed healing,” she said.Read the Philadelphia Inquirer coverage of Eva Moon’s session online.