Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers

Understanding the tumor immune microenvironment (TIME) promises to be key for optimal cancer therapy, especially in triple-negative breast cancer (TNBC). Integrating spatial resolution of immune cells with laser capture microdissection gene expression profiles, we defined distinct TIME stratification in TNBC, with implications for current therapies including immune checkpoint blockade. TNBCs with an immunoreactive microenvironment exhibited tumoral infiltration of granzyme B+CD8+ T cells (GzmB+CD8+ T cells), a type 1 IFN signature, and elevated expression of multiple immune inhibitory molecules including indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand 1 (PD-L1), and resulted in good outcomes. An “immune-cold” microenvironment with an absence of tumoral CD8+ T cells was defined by elevated expression of the immunosuppressive marker B7-H4, signatures of fibrotic stroma, and poor outcomes. A distinct poor-outcome immunomodulatory microenvironment, hitherto poorly characterized, exhibited stromal restriction of CD8+ T cells, stromal expression of PD-L1, and enrichment for signatures of cholesterol biosynthesis. Metasignatures defining these TIME subtypes allowed us to stratify TNBCs, predict outcomes, and identify potential therapeutic targets for TNBC.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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Conclusions and Perspectives In this review, we have discussed important milestones from the early description of “Serum-sickness” as being due to antibodies directed against Neu5Gc epitopes all the way to the present-day therapeutic implications of these antibodies in cancer therapy. Some of these milestones have been represented in a concise timeline (Figure 6). While the “Xenosialitis” hypothesis is well-supported in the human-like mouse models, it has yet to be conclusively proven in humans. It remains to be seen if “Xenosialitis” plays a role in other uniquely-human diseases. FI...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Yi He†, Wenyong Long† and Qing Liu* Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China Super-enhancers (SEs) refer to large clusters of enhancers that drive gene expressions. Recent data has provided novel insights in elucidating the roles of SEs in many diseases, including cancer. Many mechanisms involved in tumorigenesis and progression, ranging from internal gene mutation and rearrangement to external damage and inducement, have been demonstrated to be highly associated with SEs. Moreover, translocation, formation, deletion, or duplication of SEs themselves co...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Park M Abstract Understanding the tumor immune microenvironment (TIME) promises to be key for optimal cancer therapy, especially in triple-negative breast cancer (TNBC). Integrating spatial resolution of immune cells with laser capture microdissection gene expression profiles, we defined distinct TIME stratification in TNBC with implications for current therapies, including immune checkpoint blockade. TNBCs with an immunoreactive microenvironment exhibited tumoral infiltration of granzyme B+ CD8+ T cells, a type I interferon signature, elevated expression of multiple immune inhibitory molecules, including IDO, PD-...
Source: Clinical Breast Cancer - Category: Cancer & Oncology Authors: Tags: J Clin Invest Source Type: research
This article, however, is more of a commentary on high level strategy and the effects of regulation, coupled with a desire to forge ahead rather than hold back in the matter of treating aging, thus I concur with much more of what is said than is usually the case. For decades, one of the most debated questions in gerontology was whether aging is a disease or the norm. At present, excellent reasoning suggests aging should be defined as a disease - indeed, aging has been referred to as "normal disease." Aging is the sum of all age-related diseases and this sum is the best biomarker of aging. Aging and its d...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Journal of Internal Medicine, EarlyView.
Source: Journal of Internal Medicine - Category: Internal Medicine Authors: Source Type: research
Authors: Jung Y, Lee SJ, Lee J, Noh WC, Nam SJ, Park BW, Bae YT, Kang SS, Park HK, Yoon JH, Kim JR, Cho SH, Kim LS, Moon BI, Jung SH, Lim CW, Kim SY, Park HY, Song J, Lee KM, Park SH, Jeong J, Park HL, Kim SW, Kwak BS, Kang SH, Cho YU, Gwak GH, Park YL, Kim SW, Han S Abstract Purpose: There are few reports from Asian countries about the long-term results of aromatase inhibitor adjuvant treatment for breast cancer. This observational study aimed to evaluate the long-term effects of letrozole in postmenopausal Korean women with operable breast cancer. Methods: Self-reported quality of life (QoL) scores were seria...
Source: Journal of Breast Cancer - Category: Cancer & Oncology Tags: J Breast Cancer Source Type: research
Journal of Internal Medicine,Volume 0, Issue ja, -Not available-.
Source: Journal of Internal Medicine - Category: Internal Medicine Authors: Source Type: research
AbstractPurpose of ReviewBreast cancer therapies, such as anthracyclines, trastuzumab, and chest irradiation, have well-established cardiotoxicities that lead to adverse outcomes. Here, we will review strategies to mitigate these cardiotoxicities.Recent FindingsRecent consensus guidelines have established criteria for the identification and surveillance of breast cancer patients at increased risk of cardiotoxicity. Dose reduction, liposomal doxorubicin, and dexrazoxane may be considered in high-risk patients receiving anthracyclines. Anthracycline-free regimens should be considered in high-risk patients with HER-2+ breast ...
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research
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