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Tumor infiltrating lymphocyte breast

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https://www.readbyqxmd.com/read/28107186/the-combination-of-pd-l1-expression-and-decreased-tumor-infiltrating-lymphocytes-is-associated-with-a-poor-prognosis-in-triple-negative-breast-cancer
#1
Hitomi Mori, Makoto Kubo, Rin Yamaguchi, Reiki Nishimura, Tomofumi Osako, Nobuyuki Arima, Yasuhiro Okumura, Masayuki Okido, Mai Yamada, Masaya Kai, Junji Kishimoto, Yoshinao Oda, Masafumi Nakamura
This study included patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. Among the 248 TNBCs studied, programmed cell death ligand-1 (PD-L1) expression was detected in 103 (41.5%) tumors, and high levels of tumor-infiltrating lymphocytes (TILs) were present in 118 (47.6%) tumors. PD-L1 expression correlated with high levels of TILs, but was not a prognostic factor. Patients with TILs-high tumors had better overall survival than those with TILs-low tumors (P = 0...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28100392/replication-study-the-cd47-signal-regulatory-protein-alpha-sirpa-interaction-is-a-therapeutic-target-for-human-solid-tumors
#2
Stephen K Horrigan
In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Chroscinski et al., 2015) that described how we intended to replicate selected experiments from the paper "The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors "(Willingham et al., 2012). Here we report the results of those experiments. We found that treatment of immune competent mice bearing orthotopic breast tumors with anti-mouse CD47 antibodies resulted in short-term anemia compared to controls, consistent with the previously described function of CD47 in normal phagocytosis of aging red blood cells and results reported in the original study (Table S4; Willingham et al...
January 19, 2017: ELife
https://www.readbyqxmd.com/read/28073775/dasatinib-changes-immune-cell-profiles-concomitant-with-reduced-tumor-growth-in-several-murine-solid-tumor-models
#3
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 Yf Lee, Satu Mustjoki
Dasatinib, a broad range tyrosine kinase inhibitor (TKI), 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...
January 10, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28072971/-expression-of-pd-1-pd-l1-in-triple-negative-breast-carcinoma-and-its-significance
#4
W Zhang, G X Xu, J J Li, X Liu, Y J Chen, F Zhang
Objective: To investigate the correlation between the expression of PD-1, PD-L1 and clinicopathologic parameters in triple negative breast carcinoma (TNBC). Methods: Samples from 151 patients with TNBC and 65 cases of other breast carcinomas (non-TNBC) were examined for PD-L1 and PD-1 expression by immunohistochemical staining on tissue microarray. Results: The expression of PD-L1 and PD-1 in the tumor cells and interstitial lymphocytes in TNBC was significantly (P<0.05)higher than that in non-TNBC.In TNBC, the expression rates of PD-L1 in the cancer nests and stroma were 16...
January 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28058578/pd-l1-expression-and-tumor-infiltrating-pd-1-%C3%A2-lymphocytes-associated-with-outcome-in-her2-%C3%A2-breast-cancer-patients
#5
Julia Y S Tsang, Wai-Ling Au, Kwan-Yin Lo, Yun-Bi Ni, Thazin Hlaing, Jintao Hu, Siu-Ki Chan, Kui-Fat Chan, Sai-Yin Cheung, Gary M Tse
PURPOSE: Clinical trials showing programmed death (PD)-1-PD-ligand 1 (L1) axis as a promising therapeutic target in melanoma and non-small cell lung cancers have made the pathway a focus of recent attention. However, the data regarding PD-L1/PD-1 in breast cancer are inconsistent. Given the heterogeneity of breast cancers, the clinical relevance of PD-L1 and PD-1 tumor infiltrating lymphocytes (TIL) may vary according to subtypes of breast cancer. We aim to investigate PD-L1 expression in a large cohort of breast cancers and analyze its clinico-pathological as well as outcome relationship according to molecular subtypes...
January 5, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28052005/bortezomib-augments-lymphocyte-stimulatory-cytokine-signaling-in-the-tumor-microenvironment-to-sustain-cd8-t-cell-antitumor-function
#6
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...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28045912/claudin-low-breast-cancer-clinical-pathological-characteristics
#7
Kay Dias, Anna Dvorkin-Gheva, Robin M Hallett, Ying Wu, John Hassell, Gregory R Pond, Mark Levine, Tim Whelan, Anita L Bane
Claudin-low breast cancer is a molecular type of breast cancer originally identified by gene expression profiling and reportedly associated with poor survival. Claudin-low tumors have been recognised to preferentially display a triple-negative phenotype, however only a minority of triple-negative breast cancers are claudin-low. We sought to identify an immunohistochemical profile for claudin-low tumors that could facilitate their identification in formalin fixed paraffin embedded tumor material. First, an in silico collection of ~1600 human breast cancer expression profiles was assembled and all claudin-low tumors identified...
2017: PloS One
https://www.readbyqxmd.com/read/28039161/the-different-t-cell-receptor-repertoires-in-breast-cancer-tumors-draining-lymph-nodes-and-adjacent-tissues
#8
Ting Wang, Changxi Wang, Jinghua Wu, Chenyang He, Wei Zhang, Jiayun Liu, Ruifang Zhang, Yonggang Lv, Yongping Li, Xiaojing Zeng, Hongzhi Cao, Xiuqing Zhang, Xun Xu, Chen Huang, Ling Wang, Xiao Liu
T lymphocytes infiltrate the microenvironment of breast cancer (BC) tumors and play a pivotal role in tumor immune surveillance. Relationships between the T-cell receptors (TCRs) borne by T cells within tumors, in the surrounding tissues, and in draining lymph nodes are largely unexplored in human breast cancer. Consequently, information about the relative extent of possible T-cell exchange between these tissues is also lacking. Here we have analyzed the TCR repertoire of T cells using multiplex PCR and high throughput sequencing of the TCRβ chain in the tissues of tumor, adjacent nontumor, and axillary lymph-nodes of breast cancer patients...
December 30, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/28029650/tumor-infiltrating-lymphocytes-predict-prognosis-of-breast-cancer-patients-treated-with-anti-her-2-therapy
#9
Tan-Huan Chen, Ying-Chun Zhang, Yu-Ting Tan, Xin An, Cong Xue, Ying-Fei Deng, Wei Yang, Xia Yuan, Yan-Xia Shi
PURPOSE: Infiltration of tumor associated lymphocytes and count of its different phenotypes are potentially new independent predictor of prognosis in breast cancer. However, research related to it is less reported in breast cancer patients treated with anti-Her-2 therapy. Thus, we evaluated the relationship between survival and tumor infiltrating lymphocytes including its different phenotypes in tumors of such patients. METHODS: Between 1999 and 2010, 98 patients diagnosed with primary breast cancer and treated with anti-Her-2 therapy at Sun-Yat-Sen University Cancer Center were included in the study...
December 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/28005906/a-stromal-immune-module-correlated-with-the-response-to-neoadjuvant-chemotherapy-prognosis-and-lymphocyte-infiltration-in-her2-positive-breast-carcinoma-is-inversely-correlated-with-hormonal-pathways
#10
Anne-Sophie Hamy, Hélène Bonsang-Kitzis, Marick Lae, Matahi Moarii, Benjamin Sadacca, Alice Pinheiro, Marion Galliot, Judith Abecassis, Cecile Laurent, Fabien Reyal
INTRODUCTION: HER2-positive breast cancer (BC) is a heterogeneous group of aggressive breast cancers, the prognosis of which has greatly improved since the introduction of treatments targeting HER2. However, these tumors may display intrinsic or acquired resistance to treatment, and classifiers of HER2-positive tumors are required to improve the prediction of prognosis and to develop novel therapeutic interventions. METHODS: We analyzed 2893 primary human breast cancer samples from 21 publicly available datasets and developed a six-metagene signature on a training set of 448 HER2-positive BC...
2016: PloS One
https://www.readbyqxmd.com/read/27942588/tumor-infiltrating-lymphocytes-are-dynamically-desensitized-to-antigen-but-are-maintained-by-homeostatic-cytokine
#11
Bijan Boldajipour, Amanda Nelson, Matthew F Krummel
T cells that enter tumors are largely tolerized, but how that process is choreographed and how the ensuing "dysfunctional" tumor-infiltrating lymphocytes (TILs) are maintained are poorly understood and are difficult to assess in spontaneous disease. We exploited an autochthonous model of breast cancer for high-resolution imaging of the early and later stages of tumor residence to understand the relationships between cellular behaviors and cellular phenotypes. "Dysfunctional" differentiation began within the first days of tumor residence with an initial phase in which T cells arrest, largely on tumor-associated macrophages...
December 8, 2016: JCI Insight
https://www.readbyqxmd.com/read/27936775/inducing-optimal-antitumor-immune-response-through-coadministering-irgd-with-pirarubicin-loaded-nanostructured-lipid-carriers-for-breast-cancer-therapy
#12
Caifeng Deng, Mengdi Jia, Guangfei Wei, Tiantian Tan, Yao Fu, Huile Gao, Xun Sun, Quan Zhang, Tao Gong, Zhirong Zhang
Chemotherapeutic agents trigger antitumor immune response through inducing immunogenic tumor cell death. However, severe toxicity to immune system and insufficient immunogenic cell death hinder chemotherapy from arousing efficient antitumor immunity in vivo. In this study, the cytotoxic drug, pirarubicin (THP), was entrapped into nanostructured lipid carriers (NLC); THP-NLC significantly reduced the toxicity of THP to immune system and improved immune status of breast cancer bearing mice. When THP-NLC was coinjected with iRGD (a tumor-penetrating peptide), drug accumulation in tumors was greatly elevated, which led to significant control of tumor growth and increase of immunogenic tumor cell death...
January 3, 2017: Molecular Pharmaceutics
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
#13
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...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925176/pd-l1-expression-of-the-residual-tumor-serves-as-a-prognostic-marker-in-local-advanced-breast-cancer-after-neoadjuvant-chemotherapy
#14
Sheng Chen, Ruo-Xi Wang, Yin Liu, Wen-Tao Yang, Zhi-Ming Shao
This study sought to investigate the prevalence of programmed death ligand 1 (PD-L1) and its prognostic value in patients with residual tumors after neoadjuvant chemotherapy (NCT) for locally advanced breast cancer (LABC). A total of 309 patients considered as non-pathological complete responders (non-pCR) after NCT followed by mastectomy were selected. The expression of PD-L1 and tumor-infiltrating lymphocytes (TILs) in residual breast cancer cells was assessed by immunohistochemistry in surgical specimens...
December 7, 2016: International Journal of Cancer. Journal International du Cancer
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/27869446/-oncopathological-aspects-of-brca1-and-brca2-genes-inactivation-in-tumors-of-ovary-fallopian-tube-and-pelvic-peritoneum
#17
Petr Škapa, Pavel Dundr
Ovarian carcinoma represents a heterogeneous group of malignant epithelial tumors which could be divided into two fundamental groups: Type I (endometrioid carcinoma, clear cell carcinoma, low grade serous carcinoma, mucinous carcinoma and more rare seromucinous carcinoma and malignant Brenner tumor) and type II (high grade serous carcinoma - HGSC). HGSC is the most frequent ovarian carcinoma which may be etiologically linked to inactivation of tumor suppressor genes BRCA1/2 and TP53 and differs from type I carcinomas by higher aggressiveness, tendency to peritoneal spread and worse prognosis...
2016: Ceskoslovenská Patologie
https://www.readbyqxmd.com/read/27853639/the-ratio-of-cd8-foxp3-t-lymphocytes-infiltrating-breast-tissues-predicts-the-relapse-of-ductal-carcinoma-in-situ
#18
Michaela Semeraro, Julien Adam, Gautier Stoll, Emilie Louvet, Kariman Chaba, Vichnou Poirier-Colame, Allan Sauvat, Laura Senovilla, Erika Vacchelli, Norma Bloy, Juliette Humeau, Aitziber Buque, Oliver Kepp, Laurence Zitvogel, Fabrice André, Marie-Christine Mathieu, Suzette Delaloge, Guido Kroemer
In a series of 248 tumor samples obtained from image-guided biopsies from patients diagnosed with ductal carcinoma in situ of the breast, we attempted to identify biomarkers that predict microinfiltration at definitive surgery or relapse during follow-up. For this, we used immunohistochemical methods, followed by automated image analyses, to measure the mean diameter of nuclei (which correlates with ploidy), the phosphorylation of eukaryotic initiation factor 2α (eIF2α, which reflects endoplasmic reticulum stress) as well as the density and ratio of CD8(+) cytotoxic T lymphocytes and FOXP3(+) regulatory T cells...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27810697/lymphocyte-predominant-triple-negative-breast-carcinomas-in-premenopausal-patients-lower-expression-of-basal-immunohistochemical-markers
#19
Sergio Mitsuo Masili-Oku, Bernardo Gomes Lacerda de Almeida, Carlos Eduardo Bacchi, Jose Roberto Filassi, Edmund Chada Baracat, Filomena Marino Carvalho
OBJECTIVES: Triple-negative breast carcinomas (TNBCs) correspond to a molecular heterogeneous disease defined by lack of estrogen and progesterone receptor expression, and the absence of overexpression and/or amplification of HER2. Recent data indicate that clinical outcome in TNBC is affected by tumor-infiltrating lymphocytes, suggesting that they can benefit from immunotherapies. We selected 116 consecutive premenopausal patients with TNBC to compare the immunohistochemical profile of the group rich in tumor-infiltrating lymphocytes with those without this characteristic...
February 2017: Breast: Official Journal of the European Society of Mastology
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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