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https://www.readbyqxmd.com/read/29037255/objective-measurement-and-clinical-significance-of-ido1-protein-in-hormone-receptor-positive-breast-cancer
#1
Daniel E Carvajal-Hausdorf, Nikita Mani, Vamsidhar Velcheti, Kurt A Schalper, David L Rimm
BACKGROUND: Immunostimulatory therapies targeting immune-suppressive pathways produce durable responses in advanced solid tumors. Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting oxidoreductase that catalyzes the degradation of tryptophan to kynurenine. IDO induces immune tolerance by downregulating CD8+ and effector CD4+ T cell responses. IDO1, the most active isoform, is expressed in diverse tumor types and can be targeted using small molecule inhibitors. We used an objective, in situ assay to measure IDO1 in a collection of hormone receptor-positive breast cancers (HR+ BC)...
October 17, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28993275/the-cd4-cd8-ratio-of-tumor-infiltrating-lymphocytes-at-the-tumor-host-interface-has-prognostic-value-in-triple-negative-breast-cancer
#2
Kai Wang, Tiansheng Shen, Gene P Siegal, Shi Wei
Compelling evidence has demonstrated the prognostic value of tumor-infiltrating lymphocytes (TILs), especially in triple-negative breast cancer (TNBC). However, only a limited number of studies to investigate the importance of the subsets of T cells in TILs has been carried out, less so the significance of the location of these TILs. In this study, we explored in a cohort of 42 consecutive TNBC cases the prognostic significance of TIL subsets at the tumor-host interface (within one high power field [0.5 μm] of the invasive front) and compared them to TILs within the intratumoral stroma...
October 6, 2017: Human Pathology
https://www.readbyqxmd.com/read/28918288/th9-cells-promote-antitumor-immunity-via-il-9-and-il-21-and-demonstrate-atypical-cytokine-expression-in-breast-cancer
#3
Fa-Ping You, Jian Zhang, Tao Cui, Rui Zhu, Chong-Qing Lv, Hai-Tao Tang, Di-Wen Sun
Breast cancer is a major cause of cancer-related death in women. Antitumor T cell responses play critical therapeutic roles, including direct cytotoxicity mediated by CD8(+) T cells and immunomodulatory roles mediated by CD4(+) T cells. The IL-9-expressing Th9 cells are recently found to present antitumor immunity in melanoma and lung adenocarcinoma. In this study, we found that IL-9 expression in the serum and in circulating CD4(+) T cells were significantly upregulated in breast cancer patients compared to healthy controls...
November 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28881675/pd-l1-and-intratumoral-immune-response-in-breast-cancer
#4
Zhi-Qiang Wang, Katy Milne, Heather Derocher, John R Webb, Brad H Nelson, Peter H Watson
PURPOSE: PD-L1 is thought to play an important role in the antitumor immune response. In this study, we investigated the expression of PD-L1 within breast tumor subsets to better define its prognostic significance. METHODS: Immunohistochemistry was performed to determine PD-L1 tumor cell expression and to enumerate CD8, CD4 and CD68 tumor-infiltrating leucocytes (TIL) in a cohort of 443 breast cancers categorized by molecular subtype. RESULTS: Across the entire cohort, PD-L1 tumor cell expression was observed in 73/443 (16...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28872974/the-postoperative-immunosuppressive-phenotypes-of-peripheral-t-helper-cells-are-associated-with-poor-prognosis-of-breast-cancer-patients
#5
Ganglan Fu, Liping Miao, Meng Wang, MingYan Guo, Chengli Wang, Fengtao Ji, Minghui Cao
PURPOSE: T helper cells play essential roles in anti-tumor immune response. However, the postoperative changes of peripheral T cell subsets and their clinical significance in breast cancer patients remain largely unknown. METHODS: We evaluated the perioperative changes of T lymphocyte subsets in invasive breast cancer (IBC) patients and breast fibroadenoma (BF) patients preoperatively (preop) and 6, 24, 72 hours postoperatively (POH6, POH24, and POH72). Proportions of CD3, CD4, CD8, T helper (Th) 1, Th2, Th17 cells, regulatory T cells (Treg), and CD4(+)/CD8(+), Th1/Th2 ratio were detected by flow cytometry...
October 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28856238/reovirus-fast-protein-enhances-vesicular-stomatitis-virus-oncolytic-virotherapy-in-primary-and-metastatic-tumor-models
#6
Fabrice Le Boeuf, Simon Gebremeskel, Nichole McMullen, Han He, Anna L Greenshields, David W Hoskin, John C Bell, Brent Johnston, Chungen Pan, Roy Duncan
The reovirus fusion-associated small transmembrane (FAST) proteins are the smallest known viral fusogens (∼100-150 amino acids) and efficiently induce cell-cell fusion and syncytium formation in multiple cell types. Syncytium formation enhances cell-cell virus transmission and may also induce immunogenic cell death, a form of apoptosis that stimulates immune recognition of tumor cells. These properties suggest that FAST proteins might serve to enhance oncolytic virotherapy. The oncolytic activity of recombinant VSVΔM51 (an interferon-sensitive vesicular stomatitis virus [VSV] mutant) encoding the p14 FAST protein (VSV-p14) was compared with a similar construct encoding GFP (VSV-GFP) in cell culture and syngeneic BALB/c tumor models...
September 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28817603/expression-of-the-mhc-class-ii-in-triple-negative-breast-cancer-is-associated-with-tumor-infiltrating-lymphocytes-and-interferon-signaling
#7
In Ah Park, Seong-Hye Hwang, In Hye Song, Sun-Hee Heo, Young-Ae Kim, Won Seon Bang, Hye Seon Park, Miseon Lee, Gyungyub Gong, Hee Jin Lee
Tumor-infiltrating lymphocytes (TILs) have been known for their strong prognostic and predictive significance in triple-negative breast cancer (TNBC). Several mechanisms for TIL influx in TNBC have been elucidated. Major histocompatibility complex class II (MHC-II) is an essential component of the adaptive immune system and is generally restricted to the surface of antigen-presenting cells. However, it has been reported that interferon-gamma signaling may induce MHC-II in almost all cell types, including those derived from cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28794686/tumor-infiltrating-leukocyte-density-is-independent-of-tumor-grade-and-molecular-subtype-in-aggressive-breast-cancer-of-western-kenya
#8
Rispah T Sawe, Simeon K Mining, Ayub V Ofulla, Kirtika Patel, Bernard Guyah, David Chumba, Jenifer R Prosperi, Maggie Kerper, Zonggao Shi, Mayra Sandoval-Cooper, Katherine Taylor, Sunil Badve, M Sharon Stack, Laurie E Littlepage
BACKGROUND: Tumors commonly are infiltrated by leukocytes, or tumor infiltrating leukocytes (TILs). It remains unclear, however, if the density and type of individual TILs has a direct or simply correlative role in promoting poor prognosis in breast cancer patients. Breast cancer in Kenyan women is aggressive with presentation at a young age, with advanced grade (grade III), large tumor size (>2.0 cm), and poor prognosis. We previously observed that the tumors were predominantly estrogen receptor positive (ER+) but also included both a high percentage of triple negative tumors and also increased immune cell infiltration within the tumors...
2017: Tropical Medicine and Health
https://www.readbyqxmd.com/read/28770166/genomic-signature-of-the-natural-oncolytic-herpes-simplex-virus-hf10-and-its-therapeutic-role-in-preclinical-and-clinical-trials
#9
REVIEW
Ibrahim Ragab Eissa, Yoshinori Naoe, Itzel Bustos-Villalobos, Toru Ichinose, Maki Tanaka, Wu Zhiwen, Nobuaki Mukoyama, Taishi Morimoto, Noriyuki Miyajima, Hasegawa Hitoki, Seiji Sumigama, Branko Aleksic, Yasuhiro Kodera, Hideki Kasuya
Oncolytic viruses (OVs) are opening new possibilities in cancer therapy with their unique mechanism of selective replication within tumor cells and triggering of antitumor immune responses. HF10 is an oncolytic herpes simplex virus-1 with a unique genomic structure that has non-engineered deletions and insertions accompanied by frame-shift mutations, in contrast to the majority of engineered OVs. At the genetic level, HF10 naturally lacks the expression of UL43, UL49.5, UL55, UL56, and latency-associated transcripts, and overexpresses UL53 and UL54...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28749113/increased-tumour-infiltration-of-cd4-and-cd8-t-lymphocytes-in-patients-with-triple-negative-breast-cancer-suggests-susceptibility-to-immune-therapy
#10
Bushra Sikandar, Muhammad Asif Qureshi, Saima Naseem, Saeed Khan, Talat Mirza
Background: Patients with triple negative breast cancer (TNBC) have limited therapeutic options, largely because the complex tumour environment is not well-characterized. These patients are potential, but largely un-fathomed, candidates for immunotherapy. It is therefore highly relevant to characterize leukocyte complexity in TNBCs. Objective: To investigate leukocyte complexity in tumour environment of patients with TNBCs. Materials and methods: A total of 104 consecutive breast cancer patients undergoing mastectomy were recruited in the study after ethical approval...
July 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28736158/nanoliposomes-carrying-her2-neu-derived-peptide-ae36-with-cpg-odn-exhibit-therapeutic-and-prophylactic-activities-in-a-mice-tubo-model-of-breast-cancer
#11
Nastaran Barati, Amin Reza Nikpoor, Atefeh Razazan, Fatemeh Mosaffa, Ali Badiee, Atefeh Arab, Zahra Gholizadeh, Javad Behravan, Mahmoud Reza Jaafari
This study was designed to prepare and characterize nanoliposomal vaccine formulation encapsulating AE36 HER2/neu-derived peptide with or without CpG and evaluate the immunologic and therapeutic responses of that in BALB/c mice model of Her2 overexpressing breast cancer. AE36 was encapsulated in liposomes composed of DOTAP, DOPE and Cholesterol (DDC) or DD with. The formulations could induce both CD8+ and CD4+ responses and stimulate production of cytokines which was detected by Enzyme-linked immunospot assay (ELISpot) kits, cytotoxicity test and intracellular cytokine assay by flow cytometry...
July 21, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28680745/vaccination-targeting-human-her3-alters-the-phenotype-of-infiltrating-t-cells-and-responses-to-immune-checkpoint-inhibition
#12
Takuya Osada, Michael A Morse, Amy Hobeika, Marcio A Diniz, William R Gwin, Zachary Hartman, Junping Wei, Hongtao Guo, Xiao-Yi Yang, Cong-Xiao Liu, Kensuke Kaneko, Gloria Broadwater, H Kim Lyerly
Expression of human epidermal growth factor family member 3 (HER3), a critical heterodimerization partner with EGFR and HER2, promotes more aggressive biology in breast and other epithelial malignancies. As such, inhibiting HER3 could have broad applicability to the treatment of EGFR- and HER2-driven tumors. Although lack of a functional kinase domain limits the use of receptor tyrosine kinase inhibitors, HER3 contains antigenic targets for T cells and antibodies. Using novel human HER3 transgenic mouse models of breast cancer, we demonstrate that immunization with recombinant adenoviral vectors encoding full length human HER3 (Ad-HER3-FL) induces HER3-specific T cells and antibodies, alters the T cell infiltrate in tumors, and influences responses to immune checkpoint inhibitions...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28624814/pd-l1-and-intratumoral-immune-response-in-breast-cancer
#13
Zhi-Qiang Wang, Katy Milne, Heather Derocher, John R Webb, Brad H Nelson, Peter H Watson
PURPOSE: PD-L1 is thought to play an important role in the antitumor immune response. In this study, we investigated the expression of PD-L1 within breast tumor subsets to better define its prognostic significance. METHODS: Immunohistochemistry was performed to determine PD-L1 tumor cell expression and to enumerate CD8, CD4 and CD68 tumor-infiltrating leucocytes (TIL) in a cohort of 443 breast cancers categorized by molecular subtype. RESULTS: Across the entire cohort, PD-L1 tumor cell expression was observed in 73/443 (16...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28592566/combined-immune-checkpoint-blockade-as-a-therapeutic-strategy-for-brca1-mutated-breast-cancer
#14
Emma Nolan, Peter Savas, Antonia N Policheni, Phillip K Darcy, François Vaillant, Christopher P Mintoff, Sathana Dushyanthen, Mariam Mansour, Jia-Min B Pang, Stephen B Fox, Charles M Perou, Jane E Visvader, Daniel H D Gray, Sherene Loi, Geoffrey J Lindeman
Immune checkpoint inhibitors have emerged as a potent new class of anticancer therapy. They have changed the treatment landscape for a range of tumors, particularly those with a high mutational load. To date, however, modest results have been observed in breast cancer, where tumors are rarely hypermutated. Because BRCA1-associated tumors frequently exhibit a triple-negative phenotype with extensive lymphocyte infiltration, we explored their mutational load, immune profile, and response to checkpoint inhibition in a Brca1-deficient tumor model...
June 7, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28487507/transcriptional-regulation-of-foxp3-requires-integrated-activation-of-both-promoter-and-cns-regions-in-tumor-induced-cd8-treg-cells
#15
Sreeparna Chakraborty, Abir K Panda, Sayantan Bose, Dia Roy, Kirti Kajal, Deblina Guha, Gaurisankar Sa
T-regulatory cells are an upsurge in the tumor microenvironment and induce immune-evasion. CD4(+) Treg cells are well characterized whereas the role of CD8(+) Tregs in cancer has recently started to crease attention. Here, we report an augmentation CD8(+)FOXP3(+) Tregs in breast tumor microenvironment. FOXP3, the lineage-specific transcription factor, is a dominant regulator of Treg cell development and function. FOXP3 is induced preferentially by divergent signaling in CD4(+) Treg cells. But how FOXP3 is induced and maintained in tumor-CD8(+) Tregs is the Cinderella of the investigation...
May 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28472798/significance-of-tumor-infiltrating-lymphocytes-and-the-expression-of-topoisomerase-ii%C3%AE-in-the-prediction-of-the-clinical-outcome-of-patients-with-triple-negative-breast-cancer-after-taxane-anthracycline-based-neoadjuvant-chemotherapy
#16
Nanyan Rao, Jiayin Qiu, Jiannan Wu, Hong Zeng, Fengxi Su, Kaifeng Qiu, Junyan Wu, Herui Yao
PURPOSE: The aim of this study was to determine factors able to predict chemotherapeutic responses and clinical outcomes in patients with triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC). METHODS: Fifty-two TNBC patients on taxane-anthracycline-based NAC were included. The expression of Ki67, topoisomerase IIα (TOPOIIα), and p53, as well as the presence of CD4+ tumor-infiltrating lymphocytes (TILs) and CD8+ TILs were evaluated in biopsy specimens by immunohistochemistry...
2017: Chemotherapy
https://www.readbyqxmd.com/read/28444535/image-analysis-of-immune-cell-patterns-in-the-human-mammary-gland-during-the-menstrual-cycle-refines-lymphocytic-lobulitis
#17
Nadine S Schaadt, Juan Carlos López Alfonso, Ralf Schönmeyer, Anne Grote, Germain Forestier, Cédric Wemmert, Nicole Krönke, Mechthild Stoeckelhuber, Hans H Kreipe, Haralampos Hatzikirou, Friedrich Feuerhake
PURPOSE: To improve microscopic evaluation of immune cells relevant in breast cancer oncoimmunology, we aim at distinguishing normal infiltration patterns from lymphocytic lobulitis by advanced image analysis. We consider potential immune cell variations due to the menstrual cycle and oral contraceptives in non-neoplastic mammary gland tissue. METHODS: Lymphocyte and macrophage distributions were analyzed in the anatomical context of the resting mammary gland in immunohistochemically stained digital whole slide images obtained from 53 reduction mammoplasty specimens...
April 25, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28426268/putative-biomarkers-of-response-to-treatment-in-breast-cancer-patients-a-pilot-assay
#18
María J Rico, Herman A Perroud, Cintia Herrera, Carlos M Alasino, Eduardo A Roggero, Stella M Pezzotto, Ana Lía Nocito, Viviana R Rozados, O Graciela Scharovsky
Identifying tumor biomarkers associated with clinical behavior in breast cancer patients may allow higher accuracy in the selection of treatment. Different types of cells were determined in the primary tumors of stage I, II, and III of breast cancer patients, who were assigned to one of the two groups: (1) disease-free or (2) relapsed/progressed, at 5 years after primary treatment. We studied 32 tumor samples. CD4(+) lymphocytes and CD44(+)CD24(-/low) cells (cancer stem cells) showed a significant association with clinical outcome at 5 years of primary treatment, while CD8(+), Foxp3(+), CD34(+), and myeloid-derived suppressor cells did not show any association...
July 3, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28388539/preferential-accumulation-of-regulatory-t-cells-with-highly-immunosuppressive-characteristics-in-breast-tumor-microenvironment
#19
Azharuddin Sajid Syed Khaja, Salman M Toor, Haytham El Salhat, Issam Faour, Navid Ul Haq, Bassam R Ali, Eyad Elkord
Immunosuppressive cells such as regulatory T cells (Tregs) have an ambiguous role in breast cancer prognosis, with studies reporting both positive and negative correlations between Treg infiltration and prognosis. This discrepancy could be due to the different immunosuppressive molecules present in these cells. In the present study, we phenotypically characterize different Treg subsets infiltrating the tumor microenvironment (TME), compared to adjacent normal tissue and peripheral blood of primary breast cancer (PBC) patients...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28368410/fibroblasts-drive-an-immunosuppressive-and-growth-promoting-microenvironment-in-breast-cancer-via-secretion-of-chitinase-3-like-1
#20
N Cohen, O Shani, Y Raz, Y Sharon, D Hoffman, L Abramovitz, N Erez
Cancer-Associated Fibroblasts (CAFs) are the most prominent stromal cell type in breast tumors. CAFs promote tumor growth and metastasis by multiple mechanisms, including by mediating tumor-promoting inflammation. Immune modulation in the tumor microenvironment plays a central role in determining disease outcome. However, the functional interactions of CAFs with immune cells are largely unknown. Here we report a novel signaling axis between fibroblasts, cancer cells and immune cells in breast tumors that drives an immunosuppressive microenvironment, mediated by CAF-derived Chi3L1...
August 2017: Oncogene
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