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Tumor infiltrating lymphocyte breast

Eva Gross, Harm van Tinteren, Zhou Li, Sandra Raab, Christina Meul, Stefanie Avril, Nadja Laddach, Michaela Aubele, Corinna Propping, Apostolos Gkazepis, Manfred Schmitt, Alfons Meindl, Petra M Nederlof, Marion Kiechle, Esther H Lips
BACKGROUND: Triple-negative breast cancer (TNBC) with a BRCA1-like molecular signature has been demonstrated to remarkably respond to platinum-based chemotherapy and might be suited for a future treatment with poly(ADP-ribose)polymerase (PARP) inhibitors. In order to rapidly assess this signature we have previously developed a multiplex-ligation-dependent probe amplification (MLPA)-based assay. Here we present an independent validation of this assay to confirm its important clinical impact...
October 19, 2016: BMC Cancer
Carmen Criscitiello, Angela Esposito, Dario Trapani, Giuseppe Curigliano
It is well recognized that the immune system plays an essential role in tumor defense. The presence of tumor-infiltrating lymphocytes reflects an individual immunological response. In early breast cancer, the presence of TILs is associated with a more favorable outcome and response to therapy. In this review, we describe how TILs are assessed. Also, we discuss their role as prognostic and predictive biomarker in the neoadjuvant and adjuvant settings as well as in residual disease. Moreover, we discuss the possible implementation of TILs in daily clinical practice as well as in future clinical trials in order to fine tune prognosis and improve treatments...
October 6, 2016: Cancer Treatment Reviews
Yoon Yang Jung, Chang Lim Hyun, Min-Sun Jin, In Ae Park, Yul Ri Chung, Bobae Shim, Kyu Ho Lee, Han Suk Ryu
PURPOSE: There is no standard targeted therapy for the treatment of triple-negative breast cancer (TNBC). Therefore, its management heavily depends on adjuvant chemotherapy. Using core needle biopsy, this study evaluated the histological factors of TNBC predicting the response to chemotherapy. METHODS: One hundred forty-three TNBC patients who received single-regimen neoadjuvant chemotherapy (NAC) with the combination of doxorubicin, cyclophosphamide, and docetaxel were enrolled...
September 2016: Journal of Breast Cancer
Sang Byung Bae, Hyun Deuk Cho, Mee-Hye Oh, Ji-Hye Lee, Si-Hyong Jang, Soon Auck Hong, Junhun Cho, Sung Yong Kim, Sun Wook Han, Jong Eun Lee, Han Jo Kim, Hyun Ju Lee
PURPOSE: The interaction of programmed death receptor 1 (PD-1) and its ligand, programmed death receptor ligand 1 (PD-L1), negatively regulates immune responses. This study aimed to clarify PD-L1 expression levels in breast cancer through immunohistochemistry (IHC) and to evaluate associations between these findings and clinicopathologic variables, including prognosis. METHODS: PD-L1 expression was analyzed using IHC on tissue microarrays of 465 invasive breast carcinomas...
September 2016: Journal of Breast Cancer
Eileen E Parkes, Steven M Walker, Laura E Taggart, Nuala McCabe, Laura A Knight, Richard Wilkinson, Karen D McCloskey, Niamh E Buckley, Kienan I Savage, Manuel Salto-Tellez, Stephen McQuaid, Mary T Harte, Paul B Mullan, D Paul Harkin, Richard D Kennedy
BACKGROUND: Previously we identified a DNA damage response-deficient (DDRD) molecular subtype within breast cancer. A 44-gene assay identifying this subtype was validated as predicting benefit from DNA-damaging chemotherapy. This subtype was defined by interferon signaling. In this study, we address the mechanism of this immune response and its possible clinical significance. METHODS: We used immunohistochemistry (IHC) to characterize immune infiltration in 184 breast cancer samples, of which 65 were within the DDRD subtype...
January 2017: Journal of the National Cancer Institute
Xiaoxian Li, Ceyda Sonmez Wetherilt, Uma Krishnamurti, Jing Yang, Yamin Ma, Toncred M Styblo, Jane L Meisel, Limin Peng, Momin T Siddiqui, Cynthia Cohen, Ritu Aneja
OBJECTIVES: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, and there is no approved targeted therapy. We studied the expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in TNBC. METHODS: Full-face sections from 136 TNBC cases without neoadjuvant therapy between 2004 and 2013 were stained and evaluated for immune cell PD-1 staining and stromal or tumoral PD-L1 staining using the H-score (staining percentage × intensity)...
October 2016: American Journal of Clinical Pathology
Vassiliki Kotoula, Sotiris Lakis, Ioannis S Vlachos, Eleni Giannoulatou, Flora Zagouri, Zoi Alexopoulou, Helen Gogas, Dimitrios Pectasides, Gerasimos Aravantinos, Ioannis Efstratiou, George Pentheroudakis, Kyriaki Papadopoulou, Kyriakos Chatzopoulos, Pavlos Papakostas, Maria Sotiropoulou, Irene Nicolaou, Evangelia Razis, Amanda Psyrri, Paris Kosmidis, Christos Papadimitriou, George Fountzilas
BACKGROUND: Stromal tumor infiltrating lymphocytes (TILs) density is an outcome predictor in triple-negative breast cancer (TNBC). Herein we asked whether TILs are related to coding mutation load and to the chemical class of the resulting mutated amino acids, i.e., charged, polar, and hydrophobic mutations. METHODS: We examined paraffin tumors from TNBC patients who had been treated with adjuvant chemotherapy mostly within clinical trials (training cohort, N = 133; validation, N = 190) for phenotype concordance; TILs density; mutation load and types...
2016: PloS One
Zhonghua Zhao, Xi Chen, Shengnan Hao, Rui Jia, Nana Wang, Shaoshui Chen, Mianli Li, Chuanxin Wang, Haiting Mao
Interleukin-35 (IL-35) is a recently discovered inhibitory cytokine, which is firstly discovered to be produced by regulatory T cells (Tregs) and proposed as a key effector molecule of Treg function. This study aims to analyze the correlation between IL-35 expression in tumor-infiltrating lymphocytes (TILs) of breast cancer tissue and patients' clinical characteristics. Plasma IL-35 was also determined in 60 patients with breast invasive ductal carcinoma (IDC) and 30 healthy women by enzyme-linked immunosorbent assay...
September 24, 2016: Cytokine
E J Yoshida, Q Li, A Chung, B Knudsen, M Burnison, A J Mirhadi, Z S Zumsteg, A E Giuliano, F F Amersi, S L Shiao
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Alexandre Rouette, Assya Trofimov, David Haberl, Geneviève Boucher, Vincent-Philippe Lavallée, Giovanni D'Angelo, Josée Hébert, Guy Sauvageau, Sébastien Lemieux, Claude Perreault
Based on transcriptomic analyses of thousands of samples from The Cancer Genome Atlas, we report that expression of constitutive proteasome (CP) genes (PSMB5, PSMB6, PSMB7) and immunoproteasome (IP) genes (PSMB8, PSMB9, PSMB10) is increased in most cancer types. In breast cancer, expression of IP genes was determined by the abundance of tumor infiltrating lymphocytes and high expression of IP genes was associated with longer survival. In contrast, IP upregulation in acute myeloid leukemia (AML) was a cell-intrinsic feature that was not associated with longer survival...
2016: Scientific Reports
Silvia Darb-Esfahani, Carsten Denkert, Albrecht Stenzinger, Christoph Salat, Bruno Sinn, Christian Schem, Volker Endris, Peter Klare, Wolfgang Schmitt, Jens-Uwe Blohmer, Wilko Weichert, Markus Möbs, Hans Tesch, Sherko Kümmel, Peter Sinn, Christian Jackisch, Manfred Dietel, Toralf Reimer, Sherene Loi, Michael Untch, Gunter von Minckwitz, Valentina Nekljudova, Sibylle Loibl
BACKGROUND: TP53 mutations are frequent in breast cancer, however their clinical relevance in terms of response to chemotherapy is controversial. METHODS: 450 pre-therapeutic, formalin-fixed, paraffin-embedded core biopsies from the phase II neoadjuvant GeparSixto trial that included HER2-positive and triple negative breast cancer (TNBC) were subjected to Sanger sequencing of exons 5-8 of the TP53 gene. TP53 status was correlated to response to neoadjuvant anthracycline/taxane-based chemotherapy with or without carboplatin and trastuzumab/lapatinib in HER2-positive and bevacizumab in TNBC...
September 7, 2016: Oncotarget
Olivia C Ihedioha, Robert P C Shiu, Jude E Uzonna, Yvonne Myal
The propensity for breast cancers to elicit immune responses in patients is well established. The accumulation of tumor infiltrating lymphocytes within the primary breast tumor has been linked to better prognosis and better response to therapy. The prolactin-inducible protein (PIP) is a 15 kD protein that is expressed under physiological conditions of the breast and is regarded as a marker of mammary differentiation. While highly expressed under pathological conditions of the mammary gland, including breast cancers, PIP is expressed in very few other cancers...
October 2016: DNA and Cell Biology
Ana Paula Benaduce, Randall Brenneman, Brett Schrand, Alan Pollack, Eli Gilboa, Adrian Ishkanian
PURPOSE: To report a novel strategy using oligonucleotide aptamers to 4-1BB as an alternate method for costimulation, and show that combinatorial therapy with radiation improves the therapeutic ratio over equivalent monoclonal antibodies. METHODS AND MATERIALS: Subcutaneous 4T1 (mouse mammary carcinoma) tumors were established (approximately 100 mm(3)), and a radiation therapy (RT) dose/fractionation schedule that optimally synergizes with 4-1BB monoclonal antibody (mAb) was identified...
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Ximena Mimica, Francisco Acevedo, David Oddo, Carolina Ibáñez, Lidia Medina, Alexis Kalergis, Mauricio Camus, César Sánchez
UNLABELLED: The white blood cell count is one of the most sensitive markers associated with inflammation. The neutrophil/lymphocyte count ratio may be an independent factor for breast cancer mortality. AIM: To assess the predictive value of the neutrophil/lymphocyte ratio for mortality in breast cancer. MATERIAL AND METHODS: Review of the database of a cancer center of a University hospital. Patients with infiltrating breast cancer treated between 1997 and 2012 were selected...
June 2016: Revista Médica de Chile
David J Birnbaum, Pascal Finetti, Alexia Lopresti, Marine Gilabert, Flora Poizat, Olivier Turrini, Jean-Luc Raoul, Jean-Robert Delpero, Vincent Moutardier, Daniel Birnbaum, Emilie Mamessier, François Bertucci
Pancreatic cancer is one of the most aggressive human cancers. PD1/PDL1-inhibitors recently showed promising results in different cancers with correlation between PDL1 tumor expression and responses. Expression of programmed cell death receptor ligand 1 (PDL1) has been scarcely studied in pancreatic cancer. In this retrospective study, we analyzed PDL1 mRNA expression in 453 clinical pancreatic cancer samples profiled using DNA microarrays and RNASeq. Compared to normal pancreatic samples, PDL1 expression was upregulated in 19% of cancer samples...
August 29, 2016: Oncotarget
David B Page, Jianda Yuan, David Redmond, Y Hanna Wen, Jeremy C Durack, Ryan Emerson, Stephen Solomon, Zhiwan Dong, Phillip Wong, Christopher Comstock, Adi Diab, Janice Sung, Majid Maybody, Elizabeth Morris, Edi Brogi, Monica Morrow, Virgilio Sacchini, Olivier Elemento, Harlan Robins, Sujata Patil, James P Allison, Jedd D Wolchok, Clifford Hudis, Larry Norton, Heather L McArthur
In early-stage breast cancer, the degree of tumor-infiltrating lymphocytes (TIL) predicts response to chemotherapy and overall survival. Combination immunotherapy with immune checkpoint antibody plus tumor cryoablation can induce lymphocytic infiltrates and improve survival in mice. We used T-cell receptor (TCR) DNA sequencing to evaluate both the effect of cryoimmunotherapy in humans and the feasibility of TCR sequencing in early-stage breast cancer. In a pilot clinical trial, 18 women with early-stage breast cancer were treated preoperatively with cryoablation, single-dose anti-CTLA-4 (ipilimumab), or cryoablation + ipilimumab...
October 2016: Cancer Immunology Research
Cristina Migali, Monica Milano, Dario Trapani, Carmen Criscitiello, Angela Esposito, Marzia Locatelli, Ida Minchella, Giuseppe Curigliano
Is breast cancer (BC) immunogenic? Many data suggest that it is. Many observations demonstrated the prognostic role of tumor-infiltrating lymphocytes (TILs) in triple negative (TN) and human epidermal growth factor receptor 2 (HER-2)-positive BC. TNBCs are poorly differentiated tumors with high genetic instability and very high heterogeneity. This heterogeneity enhances the 'danger signals' and select clone variants that could be more antigenic or, in other words, that could more strongly stimulate a host immune antitumor response...
September 2016: Therapeutic Advances in Medical Oncology
Jiafeng Shou, Zhigang Zhang, Yucheng Lai, Zhigang Chen, Jian Huang
BACKGROUND: Forkhead box P3(FOXP3) is known as the optimum maker for regulatory T cells(Tregs), which are conventionally thought to induce immune tolerance to disturb the antitumor immunity. However, the research on the prognostic significance of tumor-infiltrating FOXP3+ Tregs in breast cancer is still limited and the results are controversial. METHODS: We searched for studies in PubMed, EMBASE and Web of Science prior to January 2015. The correlation between FOXP3+ tumor-infiltrating lymphocytes(TILs) and breast cancer prognosis was analyzed...
2016: BMC Cancer
Frederick S Varn, David W Mullins, Hugo Arias-Pulido, Steven Fiering, Chao Cheng
The role of the immune system in shaping cancer development and patient prognosis has recently become an area of intense focus in industry and academia. Harnessing the adaptive arm of the immune system for tumor eradication has shown great promise in a variety of tumor types. Differences between tissues, however, necessitate a greater understanding of the adaptive immunity programs that are active within each tumor type. In breast cancer, adaptive immune programs play diverse roles depending on the cellular infiltration found in each tumor...
August 26, 2016: Immunology
You Jin Ku, Hak Hee Kim, Joo Hee Cha, Hee Jung Shin, Soo Heui Baek, Hee Jin Lee, Gyungyub Gong
OBJECTIVE: Increased levels of tumor-infiltrating lymphocytes (TILs) positively correlate with the pathologic complete response rate and increased survival in patients with triple-negative breast cancer (TNBC). The purpose of this study was to investigate associations between TIL levels and MRI findings in patients with TNBC. MATERIALS AND METHODS: From February 2006 through December 2014, a total of 112 women with TNBC were selected for inclusion in the study. All lesions were evaluated by radiologists in accordance with the BI-RADS lexicon...
November 2016: AJR. American Journal of Roentgenology
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