title: IL6 Signaling in Peripheral Blood T Cells Predicts Clinical Outcome in Breast Cancer.
abstract: IL6 is a pleiotropic cytokine with both pro- and anti-inflammatory properties, which acts directly on cancer cells to promote their survival and proliferation. Elevated serum IL6 levels negatively correlate with survival of cancer patients, which is generally attributed to the direct effects of IL6 on cancer cells. How IL6 modulates the host immune response in cancer patients is unclear. Here, we show the IL6 signaling response in peripheral blood T cells is impaired in breast cancer patients and is associated with blunted Th17 differentiation. The mechanism identified involved downregulation of gp130 and IL6Rα in breast cancer patients and was independent of plasma IL6 levels. Importantly, defective IL6 signaling in peripheral blood T cells at diagnosis correlated with worse relapse-free survival. These results indicate that intact IL6 signaling in T cells is important for controlling cancer progression. Furthermore, they highlight a potential for IL6 signaling response in peripheral blood T cells at diagnosis as a predictive biomarker for clinical outcome of breast cancer patients.Cancer Res; 77(5); 1119-26. ©2016 AACR.
authors.affiliation: Department of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, California.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, California.
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Miyahira
authors.affiliation: Department of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, California.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Simons
authors.affiliation: Department of Biostatistics, University of California Los Angeles, Los Angeles, California.
authors.forename: Xuyang
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Medicine, Stanford University Medical Center, Stanford, California.
authors.forename: Andrew Y
authors.initials: AY
authors.lastname: Chang
authors.affiliation: Department of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, California.
authors.forename: Carrie
authors.initials: C
authors.lastname: Wang
authors.affiliation: BD Biosciences, San Jose, California.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Suni
authors.affiliation: BD Biosciences, San Jose, California.
authors.forename: Vernon C
authors.initials: VC
authors.lastname: Maino
authors.affiliation: Department of Surgery, Stanford University, Stanford, California.
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Dirbas
authors.affiliation: Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, California.
authors.forename: John
authors.initials: J
authors.lastname: Yim
authors.affiliation: Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California.
authors.forename: James
authors.initials: J
authors.lastname: Waisman
authors.affiliation: Department of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, California. plee@coh.org.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000276:immunology; D001943:Breast Neoplasms / Q000097:blood / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology*; D008875:Middle Aged; D015398:Signal Transduction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D015850:Interleukin-6