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Tumor infiltrating lymphocyte

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https://www.readbyqxmd.com/read/28346400/t-lymphocyte-homing-an-underappreciated-yet-critical-hurdle-for-successful-cancer-immunotherapy
#1
Robert Sackstein, Tobias Schatton, Steven R Barthel
Advances in cancer immunotherapy have offered new hope for patients with metastatic disease. This unfolding success story has been exemplified by a growing arsenal of novel immunotherapeutics, including blocking antibodies targeting immune checkpoint pathways, cancer vaccines, and adoptive cell therapy (ACT). Nonetheless, clinical benefit remains highly variable and patient-specific, in part, because all immunotherapeutic regimens vitally hinge on the capacity of endogenous and/or adoptively transferred T-effector (Teff) cells, including chimeric antigen receptor (CAR) T cells, to home efficiently into tumor target tissue...
March 27, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28345026/oncolytic-adenoviruses-armed-with-tumor-necrosis-factor-alpha-and-interleukin-2-enable-successful-adoptive-cell-therapy
#2
Riikka Havunen, Mikko Siurala, Suvi Sorsa, Susanna Grönberg-Vähä-Koskela, Michael Behr, Siri Tähtinen, João Manuel Santos, Pauliina Karell, Juuso Rusanen, Dirk M Nettelbeck, Anja Ehrhardt, Anna Kanerva, Akseli Hemminki
Adoptive cell therapy holds much promise in the treatment of cancer but results in solid tumors have been modest. The notable exception is tumor-infiltrating lymphocyte (TIL) therapy of melanoma, but this approach only works with high-dose preconditioning chemotherapy and systemic interleukin (IL)-2 postconditioning, both of which are associated with toxicities. To improve and broaden the applicability of adoptive cell transfer, we constructed oncolytic adenoviruses coding for human IL-2 (hIL2), tumor necrosis factor alpha (TNF-α), or both...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28344893/integrated-analysis-of-somatic-mutations-and-immune-microenvironment-in-malignant-pleural-mesothelioma
#3
Kazuma Kiyotani, Jae-Hyun Park, Hiroyuki Inoue, Aliya Husain, Sope Olugbile, Makda Zewde, Yusuke Nakamura, Wickii T Vigneswaran
To investigate the link between the genomic landscape of cancer cells and immune microenvironment in tumor tissues, we characterized somatic mutations and tumor-infiltrating lymphocytes (TILs) in malignant pleural mesothelioma (MPM), including mutation/neoantigen load, spatial heterogeneity of somatic mutations of cancer cells and TILs (T-cell receptor β (TCRβ) repertoire), and expression profiles of immune-related genes using specimens of three different tumor sites (anterior, posterior, and diaphragm) obtained from six MPM patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344892/clear-cell-ovarian-cancers-with-microsatellite-instability-a-unique-subset-of-ovarian-cancers-with-increased-tumor-infiltrating-lymphocytes-and-pd-1-pd-l1-expression
#4
Brooke E Howitt, Kyle C Strickland, Lynette M Sholl, Scott Rodig, Lauren L Ritterhouse, Dipanjan Chowdhury, Alan D D'Andrea, Ursula A Matulonis, Panagiotis A Konstantinopoulos
Clear cell ovarian carcinoma (CCOC) represents a distinct histologic subtype of ovarian cancer associated with significantly worse prognosis across all stages and no effective therapeutic options. Here, we report a rare but clinically important cohort of CCOCs with microsatellite instability (MSI) (MSI-CCOCs), which are highly immunogenic and may thus be very responsive to immune checkpoint blockade. CCOCs with MSI exhibit a significantly higher number of CD8(+) TILs, higher CD8(+)/CD4(+) ratio, and higher PD-1(+) TILs compared with microsatellite stable (MSS) CCOCs and compared with high grade serous ovarian cancers, which are the most common histologic subtype of ovarian cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344889/loss-of-tapasin-in-human-lung-and-colon-cancer-cells-and-escape-from-tumor-associated-antigen-specific-ctl-recognition
#5
Yosuke Shionoya, Takayuki Kanaseki, Sho Miyamoto, Serina Tokita, Ayumi Hongo, Yasuhiro Kikuchi, Vitaly Kochin, Kazue Watanabe, Ryota Horibe, Hiroshi Saijo, Tomohide Tsukahara, Yoshihiko Hirohashi, Hiroki Takahashi, Noriyuki Sato, Toshihiko Torigoe
Cytotoxic T-lymphocytes (CTLs) lyse target cells after recognizing the complexes of peptides and MHC class I molecules (pMHC I) on cell surfaces. Tapasin is an essential component of the peptide-loading complex (PLC) and its absence influences the surface repertoire of MHC class I peptides. In the present study, we assessed tapasin expression in 85 primary tumor lesions of non-small cell lung cancer (NSCLC) patients, demonstrating that tapasin expression positively correlated with patient survival. CD8(+) T-cell infiltration of tumor lesions was synergistically observed with tapasin expression and correlated positively with survival...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344887/pd-l1-galectin-9-and-cd8-tumor-infiltrating-lymphocytes-are-associated-with-survival-in-hepatocellular-carcinoma
#6
Kostandinos Sideras, Katharina Biermann, Joanne Verheij, Bart R Takkenberg, Shanta Mancham, Bettina E Hansen, Hannah M Schutz, Robert A de Man, Dave Sprengers, Sonja I Buschow, Maddy C M Verseput, Patrick P C Boor, Qiuwei Pan, Thomas M van Gulik, Turkan Terkivatan, Jan N M Ijzermans, Ulrich H W Beuers, Stefan Sleijfer, Marco J Bruno, Jaap Kwekkeboom
Novel systemic treatments for hepatocellular carcinoma (HCC) are strongly needed. Immunotherapy is a promising strategy that can induce specific antitumor immune responses. Understanding the mechanisms of immune resistance by HCC is crucial for development of suitable immunotherapeutics. We used immunohistochemistry on tissue-microarrays to examine the co-expression of the immune inhibiting molecules PD-L1, Galectin-9, HVEM and IDO, as well as tumor CD8(+) lymphocyte infiltration in HCC, in two independent cohorts of patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344882/tumor-pd-l1-expression-is-correlated-with-increased-tils-and-poor-prognosis-in-penile-squamous-cell-carcinoma
#7
Chuangzhong Deng, Zaishang Li, Shengjie Guo, Peng Chen, Xiaofeng Chen, Qianghua Zhou, Jieping Chen, Xingsu Yu, Xiaoliang Wu, Wenjuan Ma, Qiankun Xie, Yunlin Ye, Yonghong Li, Zike Qin, Zhuowei Liu, Ranyi Liu, Zhenfeng Zhang, Kai Yao, Hui Han, Fangjian Zhou
Despite its rare incidence worldwide, penile squamous cell carcinoma (PeSCC) still presents with significant morbidity and mortality due to the limited treatment options for advanced patients, especially those in developing countries. The program death-1 (PD-1)/PD-1 ligand (PD-L1) axis has been demonstrated to play an important role in tumor immune escape, and immunotherapies targeting this pathway have shown great success in certain cancer types. Here, we analyzed the expression pattern of PD-L1 in tumor cells and tumor-infiltrating lymphocytes (TILs) in PeSCC with a multi-center cohort...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344871/description-of-the-immune-microenvironment-of-chondrosarcoma-and-contribution-to-progression
#8
François A Simard, Iseulys Richert, Alexandra Vandermoeten, Anne-Valérie Decouvelaere, Jean-Philippe Michot, Christophe Caux, Jean-Yves Blay, Aurélie Dutour
Chondrosarcoma (CHS) is a rare bone malignancy characterized by its resistance to conventional systemic and radiation therapies. Whether immunotherapy targeting immune checkpoints may be active in these tumors remains unknown. To explore the role of the immune system in this tumor, we analyzed the immune environment of chondrosarcomas both in human sample, and in a syngeneic rat model, and tested the contribution of T lymphocytes and macrophages in chondrosarcoma progression. Immunohistochemical stainings were performed on human chondrosarcoma samples and on Swarm rat chondrosarcoma (SRC) model...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344863/tumor-infiltrating-lymphocytes-tils-from-patients-with-glioma
#9
Zhenjiang Liu, Qingda Meng, Jiri Bartek, Thomas Poiret, Oscar Persson, Lalit Rane, Elena Rangelova, Christopher Illies, Inti Harvey Peredo, Xiaohua Luo, Martin Vijayakumar Rao, Rebecca Axelsson Robertson, Ernest Dodoo, Markus Maeurer
Tumor-infiltrating lymphocytes (TILs) may represent a viable source of T cells for the biological treatment of patients with gliomas. Glioma tissue was obtained from 16 patients, tumor cell lines were established, and TILs were expanded in 16/16 cases using a combination of IL-2/IL-15/IL-21. Intracellular cytokine staining (ICS, IL-2, IL-17, TNFα and IFNγ production) as well as a cytotoxicity assay was used to detect TIL reactivity against autologous tumor cells or shared tumor-associated antigens (TAAs; i...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344809/basal-cell-carcinoma-pd-l1-pd-1-checkpoint-expression-and-tumor-regression-after-pd-1-blockade
#10
Evan J Lipson, Mohammed T Lilo, Aleksandra Ogurtsova, Jessica Esandrio, Haiying Xu, Patricia Brothers, Megan Schollenberger, William H Sharfman, Janis M Taube
Monoclonal antibodies that block immune regulatory proteins such as programmed death-1 (PD-1) have demonstrated remarkable efficacy in controlling the growth of multiple tumor types. Unresectable or metastatic basal cell carcinoma, however, has largely gone untested. Because PD-Ligand-1 (PD-L1) expression in other tumor types has been associated with response to anti-PD-1, we investigated the expression of PD-L1 and its association with PD-1 expression in the basal cell carcinoma tumor microenvironment. Among 40 basal cell carcinoma specimens, 9/40 (22%) demonstrated PD-L1 expression on tumor cells, and 33/40 (82%) demonstrated PD-L1 expression on tumor-infiltrating lymphocytes and associated macrophages...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28337200/metabolic-hallmarks-of-tumor-and-immune-cells-in-the-tumor-microenvironment
#11
REVIEW
Kathrin Renner, Katrin Singer, Gudrun E Koehl, Edward K Geissler, Katrin Peter, Peter J Siska, Marina Kreutz
Cytotoxic T lymphocytes and NK cells play an important role in eliminating malignant tumor cells and the number and activity of tumor-infiltrating T cells represent a good marker for tumor prognosis. Based on these findings, immunotherapy, e.g., checkpoint blockade, has received considerable attention during the last couple of years. However, for the majority of patients, immune control of their tumors is gray theory as malignant cells use effective mechanisms to outsmart the immune system. Increasing evidence suggests that changes in tumor metabolism not only ensure an effective energy supply and generation of building blocks for tumor growth but also contribute to inhibition of the antitumor response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28331757/inflammatory-myofibroblastic-tumor-of-the-breast-coexisting-with-pseudoangiomatous-stromal-hyperplasia
#12
Canan Kelten Talu, Yasemin Çakır, Ezgi Hacıhasanoğlu, Cem Leblebici, Şefika Aksoy, Mehmet Ali Nazlı
Inflammatory myofibroblastic tumors (IMTs) are uncommon breast lesions that consist of spindle cells accompanied by plasma cell-rich inflammatory infiltration, which may mimic breast cancer clinico-radiologically. A woman aged 38 years with a breast mass was referred to our general surgery clinic. The physical examination revealed a mass with irregular borders in the upper outer quadrant of the left breast. In mammography, the lesion was 15 mm in diameter with a spheric form and high density. Ultrasonographically, the mass was solid, heterogeneous, and hypoechoic with posterior enhancement...
October 2016: J Breast Health (2013)
https://www.readbyqxmd.com/read/28330372/car-t-cell-therapy-progress-and-prospects
#13
Olivia Wilkins, Allison May Keeler, Terence R Flotte
Lentivirus-mediated transduction of autologous T-cells with a chimeric antigen receptor (CAR) to confer a desired epitope-specificity as a targeted immunotherapy for cancer has been among the first human gene therapy techniques to demonstrate widespread therapeutic efficacy. Other approaches to using gene therapy to enhance anti-tumor immunity have been less specific and less effective. These included amplification, marking, and cytokine transduction of tumor infiltrating lymphocytes (TIL), recombinant virus-based expression of tumor antigens as a tumor vaccine, and transduction of antigen-presenting cells (APCs) with tumor antigens...
March 23, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28328502/spatial-statistics-for-segmenting-histological-structures-in-h-e-stained-tissue-images
#14
Luong Nguyen, A Burak Tosun, Jeffrey Fine, Adrian Lee, D Lansing Taylor, Chakra Chennubhotla
Segmenting a broad class of histological structures in transmitted light and/or fluorescence-based images is a prerequisite for determining the pathological basis of cancer, elucidating spatial interactions between histological structures in tumor microenvironments (e.g. tumor infiltrating lymphocytes), facilitating precision medicine studies with deep molecular profiling, and providing an exploratory tool for pathologists. Our paper focuses on segmenting histological structures in hematoxylin and eosin (H&E) stained images of breast tissues, e...
March 16, 2017: IEEE Transactions on Medical Imaging
https://www.readbyqxmd.com/read/28327944/a-phase-2-randomized-double-blind-placebo-%C3%A2-controlled-study-of-chemo-immunotherapy-combination-using-motolimod-with-pegylated-liposomal-doxorubicin-in-recurrent-or-persistent-ovarian-cancer-a-gynecologic-oncology-group-partners-study
#15
B J Monk, M F Brady, C Aghajanian, H A Lankes, T Rizack, J Leach, J M Fowler, R Higgins, P Hanjani, M Morgan, R Edwards, W Bradley, T Kolevska, P Foukas, E Swisher, K S Anderson, R Gottardo, J K Bryan, M Newkirk, K L Manjarrez, R S Mannel, R M Hershberg, G Coukos
Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28325361/warthin-like-papillary-renal-cell-carcinoma-clinicopathologic-morphologic-immunohistochemical-and-molecular-genetic-analysis-of-11-cases
#16
Faruk Skenderi, Monika Ulamec, Tomas Vanecek, Petr Martinek, Reza Alaghehbandan, Maria Pane Foix, Iva Babankova, Delia Perez Montiel, Isabel Alvarado-Cabrero, Marian Svajdler, Pavol Dubinský, Dana Cempirkova, Michal Pavlovsky, Semir Vranic, Ondrej Daum, Ondrej Ondic, Kristyna Pivovarcikova, Kvetoslava Michalova, Milan Hora, Pavla Rotterova, Adela Stehlikova, Martin Dusek, Michal Michal, Ondrej Hes
Oncocytic papillary renal cell carcinoma (PRCC) is a distinct subtype of PRCC, listed as a possible new variant of PRCC in the 2016 WHO classification. It is composed of papillae aligned by large single-layered eosinophilic cells showing linearly arranged oncocytoma-like nuclei. We analyzed clinicopathologic, morphologic, immunohistochemical and molecular-genetic characteristics of 11 oncocytic PRCCs with prominent tumor lymphocytic infiltrate, morphologically resembling Warthin's tumor. The patients were predominantly males (8/11, 73%), with an average age of 59years (range 14-76), and a mean tumor size of 7cm (range 1-22cm)...
April 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28325210/breast-cancer-immunology-and-immunotherapy-current-status-and-future-perspectives
#17
L de la Cruz-Merino, M Chiesa, R Caballero, F Rojo, N Palazón, F H Carrasco, V Sánchez-Margalet
Cancer immunology has gained renewed interest in the past few years due to emerging findings on mechanisms involved in tumoral immune evasion. Indisputably, immune edition is currently considered a critical hallmark of cancer. Basic research has revealed new targets which can be modulated in the clinical setting with new compounds and strategies. As recent evidence confirms, breast cancer (BC) is a complex and heterogeneous disease in which host immune responses play a substantial role. T-infiltrating lymphocytes measurement is suggested as a powerful new tool necessary to predict early BC evolution, especially in HER2-positive and triple negative subtypes...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28323742/spontaneous-regression-of-bronchial-carcinoid-is-linked-to-a-brisk-tumor-lymphocytic-infiltrate
#18
Luca Roncati, Antonio Manenti, Francesco Piscioli, Teresa Pusiol, Giuseppe Barbolini
No abstract text is available yet for this article.
April 2017: Journal of Bronchology & Interventional Pulmonology
https://www.readbyqxmd.com/read/28318336/are-tumor-infiltrating-lymphocytes-protagonists-or-background-actors-in-patient-selection-for-cancer-immunotherapy
#19
Federica Zito Marino, Paolo Antonio Ascierto, Giulio Rossi, Stefania Staibano, Marco Montella, Daniela Russo, Roberto Alfano, Alessandro Morabito, Gerardo Botti, Renato Franco
Tumor-infiltrating lymphocytes (TILs) are frequently observed in several tumors, reflecting the dynamic process of ''cancer immunoediting''. Prognostic and predictive values of TILs have been demonstrated in different cancers, proving their pivotal role in clinical outcome. In recent years, new therapies targeting immune checkpoint inhibitors, especially CTLA-4 and PD-1/PDL-1 pathways, have been introduced into clinical practice. In this context, TILs may even have a possible utility as a predictive biomarker for immunotherapy response...
March 20, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28317871/insights-into-molecular-therapy-of-glioma-current-challenges-and-next-generation-blueprint
#20
REVIEW
Y Rajesh, Ipsita Pal, Payel Banik, Sandipan Chakraborty, Sachin A Borkar, Goutam Dey, Ahona Mukherjee, Mahitosh Mandal
Glioma accounts for the majority of human brain tumors. With prevailing treatment regimens, the patients have poor survival rates. In spite of current development in mainstream glioma therapy, a cure for glioma appears to be out of reach. The infiltrative nature of glioma and acquired resistance substancially restrict the therapeutic options. Better elucidation of the complicated pathobiology of glioma and proteogenomic characterization might eventually open novel avenues for the design of more sophisticated and effective combination regimens...
March 20, 2017: Acta Pharmacologica Sinica
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