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https://www.readbyqxmd.com/read/28274688/interleukin-2-and-interleukin-10-function-synergistically-to-promote-cd8-t-cell-cytotoxicity-which-is-suppressed-by-regulatory-t-cells-in-breast-cancer
#1
Xiaogang Li, Ping Lu, Bo Li, Wanfu Zhang, Rong Yang, Yan Chu, Kaiyuan Luo
The precise role of interleukin (IL)-10 in breast cancer is not clear. Previous studies suggested a tumor-promoting role of IL-10 in breast cancer, whereas recent discoveries that IL-10 activated and expanded tumor-resident CD8(+) T cells challenged the traditional view. Here, we investigated the role of IL-10 in HLA-A2-positive breast cancer patients with Grade III, Stage IIA or IIB in-situ and invasive ductal carcinoma, and compared it with that of IL-2, the canonical CD8(+) T cell growth factor. We first observed that breast cancer patients presented higher serum levels of IL-2 and IL-10 than healthy controls...
March 5, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28250928/location-of-tumor-affects-local-and-distant-immune-cell-type-and-number
#2
Jonathan A Hensel, Vinayak Khattar, Reading Ashton, Carnellia Lee, Gene P Siegal, Selvarangan Ponnazhagan
INTRODUCTION: Tumors comprise heterogeneous populations of cells, including immune infiltrates that polarize during growth and metastasis. Our preclinical studies on breast cancer (BCa) identified functional differences in myeloid-derived suppressor cells based on tumor microenvironment (TME), prompting variations in host immune response to tumor growth, and dissemination based on tissue type. METHODS: In order to understand if such variations existed among other immune cells, and if such alteration occurs in response to tumor growth at the primary site or due to bone dissemination, we characterized immune cells, examining localized growth and in the tibia...
March 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28241844/immune-profiles-of-elderly-breast-cancer-patients-are-altered-by-chemotherapy-and-relate-to-clinical-frailty
#3
Jithendra Kini Bailur, Graham Pawelec, Sigrid Hatse, Barbara Brouwers, Ann Smeets, Patrick Neven, Annouschka Laenen, Hans Wildiers, Christopher Shipp
BACKGROUND: Effective therapeutic management of elderly patients with cancer, on an individual basis, remains a clinical challenge. Here, we identify novel biomarkers to assess elderly patients (≥70 years of age) with breast cancer undergoing treatment with or without chemotherapy. METHODS: We performed comprehensive geriatric assessment and measured markers sensitive to alteration in ageing, including leukocyte telomere length, CMV serostatus, levels of circulating growth factors and cytokines, and immune profiling of T cell and myeloid populations in blood before and at 3 months and 12 months after initiation of therapy, using flow cytometry...
February 28, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28197375/tumor-infiltrating-lymphocyte-composition-organization-and-pd-1-pd-l1-expression-are-linked-in-breast-cancer
#4
Laurence Buisseret, Soizic Garaud, Alexandre de Wind, Gert Van den Eynden, Anais Boisson, Cinzia Solinas, Chunyan Gu-Trantien, Céline Naveaux, Jean-Nicolas Lodewyckx, Hugues Duvillier, Ligia Craciun, Isabelle Veys, Denis Larsimont, Martine Piccart-Gebhart, John Stagg, Christos Sotiriou, Karen Willard-Gallo
The clinical relevance of tumor-infiltrating lymphocytes (TIL) in breast cancer (BC) has been clearly established by their demonstrated correlation with long-term positive outcomes. Nevertheless, the relationship between protective immunity, observed in some patients, and critical features of the infiltrate remains unresolved. This study examined TIL density, composition and organization together with PD-1 and PD-L1 expression in freshly collected and paraffin-embedded tissues from 125 patients with invasive primary BC...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28143493/the-yin-yan-of-ccl2-a-minor-role-in-neutrophil-anti-tumor-activity-in-vitro-but-a-major-role-on-the-outgrowth-of-metastatic-breast-cancer-lesions-in-the-lung-in-vivo
#5
Nicole Lavender, Jinming Yang, Sheau-Chiann Chen, Jiqing Sai, C Andrew Johnson, Philip Owens, Gregory D Ayers, Ann Richmond
BACKGROUND: The role of the chemokine CCL2 in breast cancer is controversial. While CCL2 recruits and activates pro-tumor macrophages, it is also reported to enhance neutrophil-mediated anti-tumor activity. Moreover, loss of CCL2 in early development enhances breast cancer progression. METHODS: To clarify these conflicting findings, we examined the ability of CCL2 to alter naïve and tumor entrained neutrophil production of ROS, release of granzyme-B, and killing of tumor cells in multiple mouse models of breast cancer...
January 31, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28126725/alterations-in-the-immune-cell-composition-in-premalignant-breast-tissue-that-precede-breast-cancer-development
#6
Amy C Degnim, Tanya L Hoskin, Muhammad Arshad, Marlene H Frost, Stacey J Winham, Rushin Brahmbhatt, Alvaro Pena, Jodi M Carter, Melody Stallings-Mann, Linda Murphy, Erin Miller, Lori Denison, Celine M Vachon, Keith L Knutson, Derek C Radisky, Daniel W Visscher
Purpose Little is known about the role of the immune system in the earliest stages of breast carcinogenesis. We studied quantitative differences in immune cell types between breast tissues from normal donors and women with benign breast disease (BBD). Design A breast tissue matched case-control study was created from donors to the Susan G. Komen® for the Cure Tissue Bank (KTB), and from women diagnosed with BBD at Mayo Clinic who either subsequently developed cancer (BBD cases) or remained cancer-free (BBD controls)...
January 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28099147/ctla-4-positive-breast-cancer-cells-suppress-dendritic-cells-maturation-and-function
#7
Xi Chen, Qianqian Shao, Shengnan Hao, Zhonghua Zhao, Yang Wang, Xiaofan Guo, Ying He, Wenjuan Gao, Haiting Mao
Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a potent immunoregulatory molecule, can down-regulate T-cell activation and inhibit anti-tumor immune response. This study showed that LPS-stimulated human dendritic cells (DCs) decreased the expression of HLA-DR, CD83 and costimulatory molecules (CD40, CD80 and CD86) following coculturing with CTLA-4+ breast cancer cells. Moreover, the suppressed DCs further inhibited proliferation of allogeneic CD4+/CD8+ T-cells, differentiation of Th1 and function of cytotoxic lymphocytes (CTLs)...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28073775/dasatinib-changes-immune-cell-profiles-concomitant-with-reduced-tumor-growth-in-several-murine-solid-tumor-models
#8
Can Hekim, Mette Ilander, Jun Yan, Erin Michaud, Richard Smykla, Markus Vähä-Koskela, Paula Savola, Siri Tähtinen, Leena Saikko, Akseli Hemminki, Panu E Kovanen, Kimmo Porkka, Francis Y F Lee, Satu Mustjoki
Dasatinib, a broad-range tyrosine kinase inhibitor, induces rapid mobilization of lymphocytes and clonal expansion of cytotoxic cells in leukemia patients. Here, we investigated whether dasatinib could induce beneficial immunomodulatory effects in solid tumor models. The effects on tumor growth and on the immune system were studied in four different syngeneic mouse models (B16.OVA melanoma, 1956 sarcoma, MC38 colon, and 4T1 breast carcinoma). Both peripheral blood (PB) and tumor samples were immunophenotyped during treatment...
February 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28053626/expression-of-t-lymphocyte-markers-in-human-epidermal-growth-factor-receptor-2-positive-breast-cancer
#9
Changro Lee, Seho Park, Joo Heung Kim, Sung Mook Lim, Hyung Seok Park, Seung Il Kim, Byeong-Woo Park
PURPOSE: The present study aimed to examine the clinical implications of CD4, CD8, and FOXP3 expression on the prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer using a web-based database, and to compare the immunohistochemical expression of T-lymphocyte markers using primary and metastatic HER2-positive tumor tissues before and after HER2-targeted therapy. METHODS: Using the cBioPortal for Cancer Genomics and Kaplan-Meier plotter, the mRNA expression, association between T-lymphocyte markers, and survival in HER2-positive cancers were investigated according to various cutoff levels...
December 2016: Journal of Breast Cancer
https://www.readbyqxmd.com/read/28052005/bortezomib-augments-lymphocyte-stimulatory-cytokine-signaling-in-the-tumor-microenvironment-to-sustain-cd8-t-cell-antitumor-function
#10
Samuel T Pellom, Duafalia F Dudimah, Menaka C Thounaojam, Roman V Uzhachenko, Ashutosh Singhal, Ann Richmond, Anil Shanker
Tumor-induced immune tolerance poses a major challenge for therapeutic interventions aimed to manage cancer. We explored approaches to overcome T-cell suppression in murine breast and kidney adenocarcinomas, and lung fibrosarcoma expressing immunogenic antigens. We observed that treatment with a reversible proteasome inhibitor bortezomib (1 mg/kg body weight) in tumor-bearing mice significantly enhanced the expression of lymphocyte-stimulatory cytokines IL-2, IL-12, and IL-15. Notably, bortezomib administration reduced pulmonary nodules of mammary adenocarcinoma 4T1...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28004985/cyclophosphamide-enhances-anti-tumor-effects-of-a-fibroblast-activation-protein-%C3%AE-based-dna-vaccine-in-tumor-bearing-mice-with-murine-breast-carcinoma
#11
Qiu Xia, Fei Geng, Fang-Fang Zhang, Chen-Lu Liu, Ping Xu, Zhen-Zhen Lu, Yu Xie, Bo Sun, Hui Wu, Bin Yu, Wei Kong, Xiang-Hui Yu, Hai-Hong Zhang
Cyclophosphamide (CY) is a DNA alkylating agent, which is widely used with other chemotherapy drugs in the treatment of various types of cancer. It can be used not only as a chemotherapeutic but also as an immunomodulatory agent to inhibit IL-10 expression and T regulatory cells (Tregs). Fibroblast activation protein α (FAPα) is expressed in cancer-associated fibroblasts in the tumor microenvironment. Immunotherapy based on FAPα, as a tumor stromal antigen, typically induces specific immune response targeting the tumor microenvironment...
February 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/27987020/bio-hmgb1-from-breast-cancer-contributes-to-m-mdsc-differentiation-from-bone-marrow-progenitor-cells-and-facilitates-conversion-of-monocytes-into-mdsc-like-cells
#12
Zhaoliang Su, Ping Ni, Peng She, Yueqin Liu, Seidu A Richard, Wenlin Xu, Haitao Zhu, Jia Wang
Myeloid-derived suppressor cells (MDSC) constitute the major cell population that regulates immune responses. They are known to accumulate in tumors, chronic inflammatory and autoimmune diseases. Previous data indicate that high mobility group box 1(HMGB1) facilitates MDSC differentiation from bone marrow, suppresses NK cells, CD4(+) and CD8(+) T cells and is involved in cancer development. However, it remains unclear what potential mechanisms of HMGB1 facilitate MDSC differentiation. In the present work, we clearly demonstrate that HMGB1 secreted by cancer cells is N-glycosylated at Asn37, which facilitates monocytic (M)-MDSC differentiation from bone marrow via the p38/NFκB/Erk1/2 pathway and also contributes to conversion of monocytes into MDSC-like cells; HMGB1 blockade by a monoclonal antibody against the HMGB1 B box obviously reduced the accumulation of M-MDSC in tumor-bearing mice, delaying tumor growth and development; additionally, MDSC expansion and HMGB1 up-regulation were also found in breast cancer patients...
March 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27974697/surrogate-in-vitro-activation-of-innate-immunity-synergizes-with-interleukin-7-to-unleash-rapid-antigen-driven-outgrowth-of-cd4-and-cd8-human-peripheral-blood-t-cells-naturally-recognizing-muc1-her2-neu-and-other-tumor-associated-antigens
#13
Latha B Pathangey, Dustin B McCurry, Sandra J Gendler, Ana L Dominguez, Jessica E Gorman, Girish Pathangey, Laurie A Mihalik, Yushe Dang, Mary L Disis, Peter A Cohen
Effective adoptive immunotherapy has proved elusive for many types of human cancer, often due to difficulties achieving robust expansion of natural tumor-specific T-cells from peripheral blood. We hypothesized that antigen-driven T-cell expansion might best be triggered in vitro by acute activation of innate immunity to mimic a life-threatening infection. Unfractionated peripheral blood mononuclear cells (PBMC) were subjected to a two-step culture, first synchronizing their exposure to exogenous antigens with aggressive surrogate activation of innate immunity, followed by γ-chain cytokine-modulated T-cell hyperexpansion...
December 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935862/targeting-of-interleukin-il-17a-inhibits-pdl1-expression-in-tumor-cells-and-induces-anticancer-immunity-in-an-estrogen-receptor-negative-murine-model-of-breast-cancer
#14
Yun-Feng Ma, Chen Chen, Dongqing Li, Min Liu, Zhuang-Wei Lv, Yanhong Ji, Jiru Xu
The expression of IL-17A and programmed death ligand 1 (PDL1) is increased in estrogen receptor-negative breast cancer. IL-17A promotes tumor cell survival and invasiveness and inhibits the antitumor immune response. The PDL1-PD1 (programmed death protein 1) signaling pathway promotes escape from immune surveillance in tumor cells. The pro-tumor properties of IL-17A and PDL1 in various cancers have been previously examined; however, the relationship and roles of IL-17A and PDL1 in ER-negative breast cancer have not been evaluated...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27913931/prognostic-value-of-tumor-infiltrating-lymphocyte-subsets-in-breast-cancer-depends-on-hormone-receptor-status
#15
Yul Ri Chung, Hyun Jeong Kim, Min Hye Jang, So Yeon Park
PURPOSE: Interaction between immune-regulatory proteins and tumor infiltrating lymphocytes (TILs) is complex, and their associations may have significant clinical implications. This study was designed to evaluate the relationships between immunomodulatory proteins and TIL subsets and their impact on prognosis in breast cancer. METHODS: 377 invasive breast cancer cases were selected, and immunohistochemistry was performed for HLA-A, HLA-ABC, and indoleamine 2,3-dioxygenase (IDO); CD4+, CD8+, and FOXP3+ T cells were counted in intratumoral and stromal areas for both absolute numbers as well as their ratios...
February 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27912781/an-immune-stratification-reveals-a-subset-of-pd-1-lag-3-double-positive-triple-negative-breast-cancers
#16
Giulia Bottai, Carlotta Raschioni, Agnese Losurdo, Luca Di Tommaso, Corrado Tinterri, Rosalba Torrisi, Jorge S Reis-Filho, Massimo Roncalli, Christos Sotiriou, Armando Santoro, Alberto Mantovani, Sherene Loi, Libero Santarpia
BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) are a robust prognostic factor in triple-negative breast cancer (TNBC). However, the clinical significance of TILs may be influenced by the complex landscape of the tumor immune microenvironment. In this study, we aimed to evaluate the composition and the functionality of lymphocytic infiltration and checkpoint receptors in TNBC. METHODS: Formalin-fixed, paraffin-embedded tissues were retrospectively collected from a cohort of patients with early-stage TNBC treated with adjuvant anthracycline-based chemotherapy (n = 259)...
December 3, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27865134/polychromatic-light-480-3400nm-similar-to-the-terrestrial-solar-spectrum-without-its-uv-component-in-post-surgical-immunorehabilitation-of-breast-cancer-patients
#17
Natalia A Zhevago, Alexander A Zimin, Tatyana V Glazanova, Natalia I Davydova, Natalia V Bychkova, Zhanna V Chubukina, Anna I Buinyakova, Marina F Ballyuzek, Kira A Samoilova
To this day, two methods of phototherapy (PT) have been successfully used in post-surgical immunorehabilitation of patients with breast cancer (BC): intravenous laser irradiation of the patients' blood and reinfusion of lympholeukosuspension of BC patients after single irradiation with HeNe laser. The objective of this pilot experimental study was to verify the effectiveness of the percutaneous use of polychromatic visible light combined with polychromatic infrared (pVIS+pIR) radiation similar to the major components of natural solar spectrum in post-surgical management of BC patients...
January 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/27858122/increased-cd14-and-decreased-cd14-populations-of-monocytes-48%C3%A2-h-after-zolendronic-acid-infusion-in-breast-cancer-patients
#18
A Kyrgidis, M P Yavropoulou, R Lagoudaki, C Andreadis, K Antoniades, D Kouvelas
It has been proposed that bisphosphonates cause osteonecrosis of the jaws through impairment of the monocyte population function and proliferation. Such changes have been confirmed in jaw tissues, ex vivo. In this clinical study, we report for the first time a similar pattern of changes in peripheral blood monocytes. INTRODUCTION: The aim of this study is to examine the effect of zolendronic acid administration in the peripheral blood white cell population, seeking a plausible pathophysiological link between bisphosphonates and osteonecrosis of the jaw...
November 17, 2016: Osteoporosis International
https://www.readbyqxmd.com/read/27787640/peripheral-t-cell-responses-to-tumour-antigens-are-associated-with-molecular-immunogenetic-and-cellular-features-of-breast-cancer-patients
#19
Nicole Janssen, Sotirios P Fortis, Lisa Speigl, Christoforos Haritos, Nectaria N Sotiriadou, Michael Sofopoulos, Niki Arnogiannaki, Catherine Stavropoulos-Giokas, Amalia Dinou, Sonia Perez, Graham Pawelec, Constantin N Baxevanis, Christopher Shipp
PURPOSE: Breast cancer is a leading cause of cancer deaths in women, but despite steady improvements in therapies, treatment is still suboptimal. Immunotherapy holds promise as a more effective therapy for breast cancer; supporting this, our prior study showed that patients possessing HER2-reactive CD8+ T cells in blood experience survival superior to patients without these cells. Here, we define a composite set of biomarkers that identify patients with T cell responses to tumour antigens...
January 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27785654/characterizing-the-immune-microenvironment-in-high-risk-ductal-carcinoma-in-situ-of-the-breast
#20
Michael J Campbell, Frederick Baehner, Tess O'Meara, Ekene Ojukwu, Booyeon Han, Rita Mukhtar, Vickram Tandon, Max Endicott, Zelos Zhu, Jasmine Wong, Gregor Krings, Alfred Au, Joe W Gray, Laura Esserman
PURPOSE: The recent increase in the incidence of ductal carcinoma in situ (DCIS) has sparked debate over the classification and treatment of this disease. Although DCIS is considered a precursor lesion to invasive breast cancer, some DCIS may have more or less risk than is realized. In this study, we characterized the immune microenvironment in DCIS to determine if immune infiltrates are predictive of recurrence. METHODS: Fifty-two cases of high-grade DCIS (HG-DCIS), enriched for large lesions and a history of recurrence, were age matched with 65 cases of non-high-grade DCIS (nHG-DCIS)...
January 2017: Breast Cancer Research and Treatment
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