IL6 Signaling in Peripheral Blood T Cells Predicts Clinical Outcome in Breast Cancer
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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.
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Kartikasari, A. E. R., Huertas, C. S., Mitchell, A., & Plebanski, M. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.692142 · Cited by 343 · see citing works
“Recent studies (108, 109) show dysregulated IL-6 secretion from peripheral T cells and dysregulated IFN-g secretion from peripheral monocytes, even from patients with only localized tumors.”
BackgroundWang, L., Simons, D. L., Lu, X., Tu, T. Y., Avalos, C., Chang, A. Y., Dirbas, F. M., Yim, J. H., Waisman, J., & Lee, P. P. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102631 · Cited by 82 · see citing works
Self-citation
- Authors
- Wang, L., Miyahira, A. K., Simons, D. L., Lu, X., Chang, A. Y., Wang, C., Suni, M. A., Maino, V. C., Dirbas, F. M., Yim, J., Waisman, J., & Lee, P. P.
- Affiliations
- City Of Hope National Medical Center (US)
- University of California, Los Angeles (US)
- Stanford Medicine (US)
- BD Biosciences (United States) (US)
- Corresponding author
- Lee, Peter P.
- ORCID
- Venue
- Cancer Research
- Published
- 2017-02-28
- Volume
- 77
- Issue
- 5
- Pages
- 1119-1126
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC5334262
- OpenAlex
- W2554729989
- Cited by
- 55
- References
- 39
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 6 · 2021: 3 · 2020: 7 · 2019: 5 · 2018: 4 · 2017: 3
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Defense Breast Cancer Research Program (W81XWH-10-1-0616, W81XWH-06-1-0417)
- NIH (5 T32 AI07290-24, R01 CA130817)
- NCI NIH (P30CA33572)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- IL-6 signaling, breast cancer, peripheral blood T cells, Th17 cell differentiation, gp130, predictive biomarkers, relapse-free survival, host immune response, cytokine signaling
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Breast Neoplasms, Female, Humans, Middle Aged, Biomarkers, Tumor, Signal Transduction, CD4-Positive T-Lymphocytes, Interleukin-6, Case-Control Studies, Treatment Outcome, Young Adult
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