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Tumor infiltrating lymphocyte breast

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https://www.readbyqxmd.com/read/28525810/tumor-infiltrating-lymphocytes-in-patients-with-her2-positive-breast-cancer-treated-with-neoadjuvant-chemotherapy-plus-trastuzumab-lapatinib-or-their-combination-a-meta-analysis-of-randomized-controlled-trials
#1
REVIEW
C Solinas, M Ceppi, M Lambertini, M Scartozzi, L Buisseret, S Garaud, D Fumagalli, E de Azambuja, R Salgado, C Sotiriou, K Willard-Gallo, M Ignatiadis
BACKGROUND: A relationship between baseline tumor-infiltrating lymphocytes (TIL) and outcomes has been described in HER2-positive breast cancer. Nevertheless, the magnitude of this association and whether this effect differs based on the type of anti-HER2 agent remain controversial. This meta-analysis investigated the association between baseline TIL and pathologic complete response (pCR) rates in HER2-positive breast cancer patients treated with neoadjuvant chemotherapy plus trastuzumab and lapatinib either alone or in combination...
May 2, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28494179/predictive-biomarkers-for-triple-negative-breast-cancer-treated-with-platinum-based-chemotherapy
#2
Juan Jin, Wenwen Zhang, Wenfei Ji, Fang Yang, Xiaoxiang Guan
Treatment of triple negative breast cancer (TNBC) has been a big challenge since it is defined. To date, platinum-based chemotherapy has played a significant role in the treatment of TNBC patients. However, some patients do not respond to platinum salts or gradually develop chemoresistance, resulting in little effect, or even some adverse effects. Here, we review numerous preclinical and clinical investigations to summarize possible mechanisms and potential predictive biomarkers of platinum in TNBC. The homologous recombination deficiency (HRD) resulting from the loss of BRCA function is the main rationale of platinum efficacy in TNBC...
May 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28488168/the-therapeutic-candidate-for-immune-checkpoint-inhibitors-elucidated-by-the-status-of-tumor-infiltrating-lymphocytes-tils-and-programmed-death-ligand-1-pd-l1-expression-in-triple-negative-breast-cancer-tnbc
#3
Nobumoto Tomioka, Manabu Azuma, Mayuko Ikarashi, Mitsugu Yamamoto, Masako Sato, Ken-Ichi Watanabe, Katsushige Yamashiro, Masato Takahashi
BACKGROUND: The status of tumor-infiltrating lymphocytes (TILs) is a prognostic factor for triple negative breast cancer (TNBC). Recent studies have shown that programmed cell death 1 (PD-1) or programmed death ligand 1 (PD-L1) is expressed on T lymphocytes or tumor cells modulating antitumor immunity. The regulation of immune checkpoints between tumor cells and T lymphocytes may serve as a target for improvement of TNBC prognosis. We investigated TILs and PD-L1 status in TNBCs before or after preoperative systemic therapy (PST) to elucidate the clinical significance of PD-L1 expression...
May 9, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28473315/4-1bb-enhanced-expansion-of-cd8-til-from-triple-negative-breast-cancer-unveils-mutation-specific-cd8-t-cells
#4
Michiko Harao, Marie-Andrée Forget, Jason Roszik, Hui Gao, Gildy V Babiera, Savitri Krishnamurthy, Jessica A Chacon, Shumin Li, Elizabeth A Mittendorf, Sarah M DeSnyder, Korrene F Rockwood, Chantale Bernatchez, Naoto T Ueno, Laszlo G Radvanyi, Luis Vence, Cara Haymaker, James M Reuben
Triple negative breast cancer (TNBC) highly infiltrated with CD8(+) tumor-infiltrating lymphocytes (TILs) has been associated with improved prognosis. This observation led us to hypothesize that CD8(+) TIL could be utilized in autologous adoptive cell therapy for TNBC, although this concept has proven to be challenging, given the difficulty in expanding CD8(+) TILs in solid cancers other than melanoma. To overcome this obstacle, we used an agonistic antibody  (urelumab) to a TNFR family member, 4-1BB/CD137, which is expressed by recently activated CD8(+) T cells...
May 4, 2017: Cancer Immunology Research
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
#5
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...
May 5, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28432397/downregulation-of-neuropilin-1-on-macrophages-modulates-antibody-mediated-tumoricidal-activity
#6
Kosuke Kawaguchi, Eiji Suzuki, Mariko Nishie, Isao Kii, Tatsuki R Kataoka, Masahiro Hirata, Masashi Inoue, Fengling Pu, Keiko Iwaisako, Moe Tsuda, Ayane Yamaguchi, Hironori Haga, Masatoshi Hagiwara, Masakazu Toi
Neuropilin-1 (NRP-1)-expressing macrophages are engaged in antitumor immune functions via various mechanisms. In this study, we investigated the role of NRP-1 on macrophages in antibody-mediated tumoricidal activity. Treatment of macrophages with NRP-1 knockdown or an anti-NRP-1-neutralizing antibody significantly suppressed antibody-dependent cellular cytotoxicity and modulated cytokine secretion from macrophages in vitro. Furthermore, in vivo studies using a humanized mouse model bearing human epidermal growth factor receptor-2 (HER2)-positive breast cancer xenografts showed that antibody-mediated antitumor activity and tumor infiltration of CD4(+) T lymphocytes were significantly downregulated when peripheral blood mononuclear cells in which NRP-1 was knocked down were co-administered with an anti-HER2 antibody...
April 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28430349/prognostic-significance-of-infiltrating-immune-cell-subtypes-in-invasive-ductal-carcinoma-of-the-breast
#7
Yangmei Xu, Suzhen Lan, Qiuhong Zheng
PURPOSE: To explore the correlation between tumor-infiltrating immune cell subsets and breast cancer prognosis. MATERIALS AND METHODS: Specimens of 102 patients with invasive ductal carcinoma of the breast were analyzed for immune-related markers (CD8, CD20, FOXP3 and CD68). The number of positive cells in the 3 most highly stained intratumoral stroma areas of the primary tumor was counted. The mean number was calculated and used to divide patients into 2 groups for each marker (CD8-high/CD8-low, CD20-high/CD20-low, FOXP3-high/FOXP3-low, and CD68-high/CD68-low)...
April 20, 2017: Tumori
https://www.readbyqxmd.com/read/28428277/immune-gene-expression-is-associated-with-genomic-aberrations-in-breast-cancer
#8
Anton Safonov, Tingting Jiang, Giampaolo Bianchini, Balázs Győrffy, Thomas Karn, Christos Hatzis, Lajos Pusztai
The presence of tumor-infiltrating lymphocytes (TIL) is a favorable prognostic factor in breast cancer, but what drives immune infiltration remains unknown. Here we examine if clonal heterogeneity, total mutation load, neoantigen load, copy number variations (CNV), gene- or pathway-level somatic mutations, or germline polymorphisms (SNP) are associated with immune metagene expression in breast cancer subtypes. Thirteen published immune metagenes correlated separately with genomic metrics in the 3 major breast cancer subtypes...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28426105/the-prevalence-and-clinical-relevance-of-tumor-infiltrating-lymphocytes-tils-in-ductal-carcinoma-in-situ-of-the-breast
#9
G Pruneri, M Lazzeroni, V Bagnardi, G B Tiburzio, N Rotmensz, A DeCensi, A Guerrieri-Gonzaga, A Vingiani, G Curigliano, S Zurrida, F Bassi, R Salgado, G Van den Eynden, S Loi, C Denkert, B Bonanni, G Viale
Background: Tumor-infiltrating lymphocytes (TILs) are a robust prognostic adjunct in invasive breast cancer, but their clinical role in ductal carcinoma in situ (DCIS) has not been ascertained. Patients and methods: We evaluated the prevalence and clinical relevance of TILs in a well annotated series of 1488 consecutive DCIS women with a median follow-up of 8.2 years. Detailed criteria for TILs evaluation were pre-defined involving the International Immuno-Oncology Biomarker Working Group...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28422766/an-immunoscore-using-pd-l1-cd68-and-tumor-infiltrating-lymphocytes-tils-to-predict-response-to-neoadjuvant-chemotherapy-in-invasive-breast-cancer
#10
Lauren E McLemore, Murali Janakiram, Joseph Albanese, Nella Shapiro, Yungtai Lo, Xingxing Zang, Susan Fineberg
Response to neoadjuvant chemotherapy (NAC) in invasive breast cancer (IBC) is partly regulated by the immune microenvironment. We evaluated immune checkpoint PD-L1 expression, presence of CD68+ cells of macrophage/monocytic lineage and stromal tumor-infiltrating lymphocytes (TILs) in prechemotherapy biopsies and correlated with NAC response. We studied 76 cases of IBC. Prechemotherapy biopsies with >30% TILs were considered lymphocyte-rich IBC. We performed immunohistochemistry for PD-L1 and CD68. Prechemotherapy cores showing >1% PD-L1+ immune or tumor cells were considered positive...
April 18, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28416734/the-angiotensin-receptor-blocker-losartan-inhibits-mammary-tumor-development-and-progression-to-invasive-carcinoma
#11
Rhiannon Coulson, Seng H Liew, Angela A Connelly, Nicholas S Yee, Siddhartha Deb, Beena Kumar, Ana C Vargas, Sandra A O'Toole, Adam C Parslow, Ashleigh Poh, Tracy Putoczki, Riley J Morrow, Mariah Alorro, Kyren A Lazarus, Evie F W Yeap, Kelly L Walton, Craig A Harrison, Natalie J Hannan, Amee J George, Colin D Clyne, Matthias Ernst, Andrew M Allen, Ashwini L Chand
Drugs that target the Renin-Angiotensin System (RAS) have recently come into focus for their potential utility as cancer treatments. The use of Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) Inhibitors (ACEIs) to manage hypertension in cancer patients is correlated with improved survival outcomes for renal, prostate, breast and small cell lung cancer. Previous studies demonstrate that the Angiotensin Receptor Type I (AT1R) is linked to breast cancer pathogenesis, with unbiased analysis of gene-expression studies identifying significant up-regulation of AGTR1, the gene encoding AT1R in ER+ve/HER2-ve tumors correlating with poor prognosis...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405516/assessment-of-tumor-infiltrating-tcrv%C3%AE-9v%C3%AE-2-%C3%AE-%C3%AE-lymphocyte-abundance-by-deconvolution-of-human-cancers-microarrays
#12
Marie Tosolini, Frédéric Pont, Mary Poupot, François Vergez, Marie-Laure Nicolau-Travers, David Vermijlen, Jean-Emmanuel Sarry, Francesco Dieli, Jean-Jacques Fournié
Most human blood γδ cells are cytolytic TCRVγ9Vδ2(+) lymphocytes with antitumor activity. They are currently investigated in several clinical trials of cancer immunotherapy but so far, their tumor infiltration has not been systematically explored across human cancers. Novel algorithms allowing the deconvolution of bulk tumor transcriptomes to find the relative proportions of infiltrating leucocytes, such as CIBERSORT, should be appropriate for this aim but in practice they fail to accurately recognize γδ T lymphocytes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28405507/a-review-of-the-importance-of-immune-responses-in-luminal-b-breast-cancer
#13
REVIEW
Delia J Nelson, Briony Clark, Kylie Munyard, Vincent Williams, David Groth, Jespal Gill, Henry Preston, Arlene Chan
Historically, the immune environment was not considered an important target for breast cancer treatment. However, the association of lymphocytic infiltrates in triple negative and HER-2 over-amplified breast cancer subtypes with better outcomes, has provoked interest in evaluating the role of the immune system in the luminal B subtype that accounts for 39% of breast cancers and has a poor patient prognosis. It is unknown which immunosuppressive cell types or molecules (e.g., checkpoint molecules) are relevant, or where measurement is most informative...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28405497/results-of-a-phase-i-ii-study-of-adjuvant-concurrent-carboplatin-and-accelerated-radiotherapy-for-triple-negative-breast-cancer
#14
Silvia C Formenti, Encouse B Golden, Judith D Goldberg, Xiaochun Li, Jessica Taff, Maria B Fenton-Kerimian, Sharanya Chandrasekhar, Sandra Demaria, Yelena Novik
Purpose: To determine feasibility and explore the clinical efficacy of concurrent radiotherapy and carboplatin as adjuvant treatment of triple negative breast cancer (TNBC). Patients and Methods: Women with Stage I-II TNBC were treated after surgery in a phase I-II prospective trial [NCT01289353]. Weekly carboplatin (AUC = 2.0) was delivered for 6 weeks. Concurrent radiotherapy was delivered in the prone position during weeks 2-4, for a total dose of 40.5 Gy in 15 fractions to the breast, and 46.5 Gy in 17 fractions to the tumor bed...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28404866/combined-antiangiogenic-and-anti-pd-l1-therapy-stimulates-tumor-immunity-through-hev-formation
#15
Elizabeth Allen, Arnaud Jabouille, Lee B Rivera, Inge Lodewijckx, Rindert Missiaen, Veronica Steri, Kevin Feyen, Jaime Tawney, Douglas Hanahan, Iacovos P Michael, Gabriele Bergers
Inhibitors of VEGF (vascular endothelial growth factor)/VEGFR2 (vascular endothelial growth factor receptor 2) are commonly used in the clinic, but their beneficial effects are only observed in a subset of patients and limited by induction of diverse relapse mechanisms. We describe the up-regulation of an adaptive immunosuppressive pathway during antiangiogenic therapy, by which PD-L1 (programmed cell death ligand 1), the ligand of the negative immune checkpoint regulator PD-1 (programmed cell death protein 1), is enhanced by interferon-γ-expressing T cells in distinct intratumoral cell types in refractory pancreatic, breast, and brain tumor mouse models...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28399903/overexpression-of-syndecan-1-muc-1-and-putative-stem-cell-markers-in-breast-cancer-leptomeningeal-metastasis-a-cerebrospinal-fluid-flow-cytometry-study
#16
Iole Cordone, Serena Masi, Valentina Summa, Mariantonia Carosi, Antonello Vidiri, Alessandra Fabi, Alessia Pasquale, Laura Conti, Immacolata Rosito, Carmine Maria Carapella, Veronica Villani, Andrea Pace
BACKGROUND: Cancer is a mosaic of tumor cell subpopulations, where only a minority is responsible for disease recurrence and cancer invasiveness. We focused on one of the most aggressive circulating tumor cells (CTCs) which, from the primitive tumor, spreads to the central nervous system (CNS), evaluating the expression of prognostic and putative cancer stem cell markers in breast cancer (BC) leptomeningeal metastasis (LM). METHODS: Flow cytometry immunophenotypic analysis of cerebrospinal fluid (CSF) samples (4...
April 11, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28387539/expression-of-phosphorylated-hippo-pathway-kinases-mst1-2-and-lats1-2-in-her2-positive-and-triple-negative-breast-cancer-patients-treated-with-neoadjuvant-therapy
#17
Cristiana Ercolani, Anna Di Benedetto, Irene Terrenato, Laura Pizzuti, Luigi Di Lauro, Domenico Sergi, Francesca Sperati, Simonetta Buglioni, Maria Teresa Ramieri, Lucia Mentuccia, Teresa Gamucci, Letizia Perracchio, Edoardo Pescarmona, Marcella Mottolese, Maddalena Barba, Patrizia Vici, Ruggero De Maria, Marcello Maugeri-Saccà
The Hippo kinases MST1/2 and LATS1/2 inhibit the oncoproteins TAZ/YAP and regulate T cell function. Hippo kinases also cooperate with the ATR-Chk1 and ATM-Chk2 pathways, central orchestrators of the DNA damage response (DDR). We hypothesized that MST1/2 and LATS1/2 localization differently impacts the efficacy of neoadjuvant therapy (NAT) in breast cancer, being protective when expressed in the cytoplasm of tumor cells and in tumor-infiltrating lymphocytes, whereas representing molecular determinants of chemoresistance when present in the nucleus as a consequence of their cooperation with the DDR...
April 7, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28378631/tumor-infiltrating-lymphocytes-and-breast-cancer-beyond-the-prognostic-and-predictive-utility
#18
REVIEW
Andrea Ravelli, Giandomenico Roviello, Daniele Cretella, Andrea Cavazzoni, Alessandra Biondi, Maria Rosa Cappelletti, Laura Zanotti, Giuseppina Ferrero, Marco Ungari, Fabrizio Zanconati, Alberto Bottini, Roberta Alfieri, Pier Giorgio Petronini, Daniele Generali
The importance of the immune system as a potent anti-tumor defense has been consolidated in recent times, and novel immune-related therapies are today demonstrating a strong clinical benefit in the setting of several solid neoplasms. Tumor-infiltrating lymphocytes reflect the attempt of the host to eradicate malignancies, and during the last decades, they have been shown to possess an interesting prognostic utility for breast cancer, especially in case of HER2 positive and triple-negative molecular subtypes...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28377481/characterization-of-an-immunogenic-mutation-in-a-patient-with-metastatic-triple-negative-breast-cancer
#19
Yasmine Assadipour, Nikolaos Zacharakis, Jessica S Crystal, Todd D Prickett, Jared J Gartner, Robert P T Somerville, Hui Xu, Mary A Black, Li Jia, Harshini Chinnasamy, Isaac Kriley, Lily Lu, John R Wunderlich, Zhili Zheng, Yong-Chen Lu, Paul F Robbins, Steven A Rosenberg, Stephanie L Goff, Steven A Feldman
The administration of autologous tumor infiltrating lymphocytes (TIL) can mediate durable tumor regressions in patients with melanoma likely based on the recognition of immunogenic somatic mutations expressed by the cancer. There is limited data regarding the immunogenicity of mutations in breast cancer. We sought to identify immunogenic non-synonymous mutations in a patient with triple-negative breast cancer (TNBC) in order to identify and isolate mutation-reactive TIL for possible use in adoptive cell transfer...
April 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28374322/erratum-to-tumor-infiltrating-lymphocytes-and-molecular-response-after-neoadjuvant-therapy-for-hr-her2-%C3%A2-breast-cancer-results-from-two-prospective-trials
#20
M V Dieci, A Frassoldati, D Generali, G Bisagni, F Piacentini, L Cavanna, K Cagossi, F Puglisi, A Michelotti, R Berardi, G Banna, A Goubar, G Ficarra, G Griguolo, Pierfranco Conte, V Guarneri
No abstract text is available yet for this article.
April 3, 2017: Breast Cancer Research and Treatment
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