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tumor infiltrating t lymphocyte

Joseph M Obeid, Nolan A Wages, Yinin Hu, Donna H Deacon, Craig L Slingluff
INTRODUCTION: Infiltration of non-small-cell lung cancer (NSCLC) by CD8(+) T lymphocytes predicts improved patient survival; however, heterogeneity of intratumoral localization complicates this assessment. Strategies for tumor sampling may not accurately represent the whole tumor. We hypothesized that sampling strategies may alter the identification of tumors with high CD8 density and affect the prognostic significance. PATIENTS AND METHODS: Twenty-three primary NSCLC tumors were immunohistochemically stained for CD8 and were assessed using automated software with eight different sampling strategies or the whole tumor...
October 21, 2016: Cancer Immunology, Immunotherapy: CII
H Kumon, Y Ariyoshi, K Sasaki, T Sadahira, M Araki, S Ebara, H Yanai, M Watanabe, Y Nasu
As the First-In-Human study of in situ gene therapy using an adenovirus vector carrying the human REIC (reduced expression in immortalized cell)/Dkk-3 gene (Ad-REIC), we conducted neoadjuvant intraprostatic injections in patients with high-risk localized prostate cancer undergoing radical prostatectomy (RP). Patients with recurrence probability of 35% or more within 5 years following RP, as calculated by Kattan's nomogram, were enrolled. Patients received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection...
October 21, 2016: Cancer Gene Therapy
Hui Han, Jinzhou Zhu, Yaqiong Wang, Zhengbin Zhu, Yanjia Chen, Lin Lu, Wei Jin, Xiaoxiang Yan, Ruiyan Zhang
Renal fibrosis is a significant threat to public health globally. Diverse primary aetiologies eventually result in chronic kidney disease (CKD) and immune cells influence this process. The roles of monocytes/macrophages, T cells and mast cells have been carefully examined, whilst only a few studies have focused on the effect of B cells. We investigated B cell function in tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO), using genetic B cell-deficient μMT mice or CD20 antibody-mediated B cell depleted mice...
October 20, 2016: Journal of Pathology
Sarah A Weiss, Joseph Han, Farbod Darvishian, Jeremy Tchack, Sung Won Han, Karolina Malecek, Michelle Krogsgaard, Iman Osman, Judy Zhong
BACKGROUND: Age has been reported as an independent prognostic factor for melanoma-specific survival (MSS). We tested the hypothesis that age impacts the host anti-tumor immune response, accounting for age-specific survival outcomes in three unique melanoma patient cohorts. METHODS: We queried the U.S. population-based Surveillance, Epidemiology, and End Results Program (SEER), the prospective tertiary care hospital-based Interdisciplinary Melanoma Cooperative Group (IMCG) biorepository, and the Cancer Genome Atlas (TCGA) biospecimen database to test the association of patient age at time of melanoma diagnosis with clinicopathologic features and survival outcomes...
October 19, 2016: Journal of Translational Medicine
Giang Huong Nguyen, James Y Wang, Kenneth B Hymes, Cynthia M Magro
Adult T-cell leukemia/lymphoma (ATLL) is a rare and often aggressive lymphoid malignancy known to be associated with human T-cell lymphotropic virus type 1. There are 2 broad categories: acute and chronic. In the acute category, there is a leukemic and a lymphomatous variant, whereas in the designated "chronic" form, there is mild peripheral blood lymphocytosis. The intermediate "smoldering" category is without peripheral blood lymphocytosis with only discernible skin involvement. We present a 68-year-old human T-cell lymphotropic virus type 1 seropositive female with a mild peripheral blood atypical lymphocytosis who had indurated nodules on her hands of 2 years duration and a new scaly ichthyosiform eruption on her lower extremities...
October 12, 2016: American Journal of Dermatopathology
Aikaterini Hatzioannou, Saba Nayar, Anastasios Gaitanis, Francesca Barone, Constantinos Anagnostopoulos, Panayotis Verginis
The beneficial effects of checkpoint blockade in tumor immunotherapy are limited to patients with increased tumor-infiltrating lymphocytes (TILs). Delineation of the regulatory networks that orchestrate the presence of TILs holds great promise for the design of effective immunotherapies. Podoplanin/gp38 (PDPN)-expressing lymph node stromal cells (LNSCs) are present in tumor stroma; however, their effect in the regulation of TILs remains elusive. Herein we demonstrate that intratumor injection of ex-vivo-isolated PDPN(+) LNSCs into melanoma-bearing mice induces elimination of TILs and promotes tumor growth...
2016: Oncoimmunology
Hiroyuki Inoue, Jae-Hyun Park, Kazuma Kiyotani, Makda Zewde, Azusa Miyashita, Masatoshi Jinnin, Yukiko Kiniwa, Ryuhei Okuyama, Ryota Tanaka, Yasuhiro Fujisawa, Hiroshi Kato, Akimichi Morita, Jun Asai, Norito Katoh, Kenji Yokota, Masashi Akiyama, Hironobu Ihn, Satoshi Fukushima, Yusuke Nakamura
Immune checkpoint inhibitors blocking the interaction between programmed death-1 (PD-1) and PD-1 ligand-1 (PD-L1) are revolutionizing the cancer immunotherapies with durable clinical responses. Although high expression of PD-L1 in tumor tissues has been implicated to correlate with the better response to the anti-PD-1 therapies, this association has been controversial. In this study, to characterize immune microenvironment in tumors, we examined mRNA levels of immune-related genes and characterized T cell repertoire in the tumors of 13 melanoma patients before and after nivolumab treatment...
2016: Oncoimmunology
Qiong Liu, Wen Wen, Liang Tang, Chen-Jie Qin, Yan Lin, Hui-Lu Zhang, Han Wu, Charles Ashton, Hong-Ping Wu, Jin Ding, Wei Dong, Le-Xing Yu, Wen Yang, Dan-Dan Huang, Meng-Chao Wu, Hong-Yang Wang, He-Xin Yan
Despite their central function in tumor immunity, dendritic cells (DCs) can respond to inhibitory signals and become tolerogenic, curtailing T cell responses in vivo. Here, we provide the evidence for an inhibitory function of signal regulatory protein (SIRP) α in DC survival and activation. In tumors from human liver cancer patients, infiltrative DCs expressed elevated levels of SIRPα, which is correlated with the induction of immune tolerance within the tumors. Silencing of SIRPα resulted in a significant increase in the longevity of antigen-pulsed DCs in the draining lymph nodes...
2016: Oncoimmunology
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
Hirotsugu Nagase, Tomohira Takeoka, Shinya Urakawa, Akiko Morimoto-Okazawa, Atsunari Kawashima, Kota Iwahori, Shuji Takiguchi, Hiroyoshi Nishikawa, Eiichi Sato, Shimon Sakaguchi, Masaki Mori, Yuichiro Doki, Hisashi Wada
Regulatory T cells (Tregs) have an immunosuppressive role in the tumor microenvironment. Since effector Tregs (eTregs), which have highly suppressive functions, are located in a subpopulation of Foxp3(+) CD4(+) Tregs, the TCR-inducible costimulatory receptor (ICOS) was applied as a marker of eTregs that infiltrated gastric cancer tissue and the induction pathway of ICOS(+) Foxp3(+) cells was analyzed by flow cytometry and immunohistochemistry. In tumor-infiltrating lymphocytes (TILs), ICOS(+) Foxp3(+) CD4(+) T cells were abundantly observed in the late stages of gastric cancer...
October 18, 2016: International Journal of Cancer. Journal International du Cancer
Mahzad Akbarpour, Abdelnaby Khalyfa, Zhuanghong Qiao, Alex Gileles-Hillel, Isaac Almendros, Ramon Farré, David Gozal
STUDY OBJECTIVE: The presence of obstructive sleep apnea (OSA) in patients with cancer appears to be accompanied by poorer outcomes. However, the mechanisms underlying such association are unknown. Tumor infiltrating lymphocytes (TILs), including CD8+ T cells, function as cytotoxic T lymphocytes (CTLs), and mount immune responses to cancer by the release of cytolytic enzymes, including granzyme B (GzmB), perforin (Prf) and cytokines such as interferon (IFN)-γ. METHODS: Using established in vivo mouse models, we investigated CD8+ T cells and cancer stem cells (CSC) in intermittent hypoxia (IH) and sleep fragmentation (SF) in the context of tumor environment...
October 10, 2016: Sleep
Hyeyoon Chang, Woon Yong Jung, Youngran Kang, Hyunjoo Lee, Aeree Kim, Han Kyeom Kim, Bong Kyung Shin, Baek-Hui Kim
Gastric adenocarcinoma is one of the most common causes of cancer-related death. In this study, we conducted immunohistochemical studies for PD-L1, PD-1, CTLA-4, and CD8 using tissue microarrays from 464 gastric cancer samples and evaluated the correlations between their expression, clinicopathologic factors, and five-year overall survival. PD-L1 and PD-1 expression was significantly correlated with several adverse prognostic pathologic factors, including higher T-stage, diffuse Lauren histologic type, and lymphatic invasion...
October 12, 2016: Oncotarget
Siri Tähtinen, Carolin Blattner, Markus Vähä-Koskela, Dipongkor Saha, Mikko Siurala, Suvi Parviainen, Jochen Utikal, Anna Kanerva, Viktor Umansky, Akseli Hemminki
The immunosuppressive microenvironment of solid tumors renders adoptively transferred T cells hypofunctional. However, adenoviral delivery of immunostimulatory cytokines IL2 and TNFα can significantly improve the efficacy of adoptive T-cell therapy. Using ret transgenic mice that spontaneously develop skin malignant melanoma, we analyzed the mechanism of action of adenoviruses coding for IL2 and TNFα in combination with adoptive transfer of TCR-transgenic TRP-2-specific T cells. Following T-cell therapy and intratumoral virus injection, a significant increase in antigen-experienced, tumor-reactive PD-1 CD8 T cells was seen in both cutaneous lesions and in metastatic lymph nodes...
November 2016: Journal of Immunotherapy
Ruoxu Dou, Reiko Nishihara, Yin Cao, Tsuyoshi Hamada, Kosuke Mima, Atsuhiro Masuda, Yohei Masugi, Yan Shi, Mancang Gu, Wanwan Li, Annacarolina da Silva, Katsuhiko Nosho, Xuehong Zhang, Jeffrey A Meyerhardt, Edward L Giovannucci, Andrew T Chan, Charles S Fuchs, Zhi Rong Qian, Shuji Ogino
Experimental evidence suggests that the let-7 family of noncoding RNAs suppresses adaptive immune responses, contributing to immune evasion by the tumor. We hypothesized that the amount of let-7a and let-7b expression in colorectal carcinoma might be associated with limited T-lymphocyte infiltrates in the tumor microenvironment and worse clinical outcome. Utilizing the molecular pathological epidemiology resources of 795 rectal and colon cancers in two U.S.-nationwide prospective cohort studies, we measured tumor-associated let-7a and let-7b expression levels by quantitative reverse-transcription PCR, and CD3(+), CD8(+), CD45RO (PTPRC)(+), and FOXP3(+) cell densities by tumor tissue microarray immunohistochemistry and computer-assisted image analysis...
October 13, 2016: Cancer Immunology Research
R Krishnan Kutty, William Samuel, Kaifa Boyce, Aswini Cherukuri, Todd Duncan, Cynthia Jaworski, Chandrasekharam N Nagineni, T Michael Redmond
PURPOSE: Proinflammatory cytokines interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β) secreted by infiltrating lymphocytes or macrophages may play a role in triggering RPE dysfunction associated with age-related macular degeneration (AMD). Binding of these proinflammatory cytokines to their specific receptors residing on the RPE cell surface can activate signaling pathways that, in turn, may dysregulate cellular gene expression. The purpose of the present study was to investigate whether IFN-γ, TNF-α, and IL-1β have an adverse effect on the expression of genes essential for RPE function, employing the RPE cell line ARPE-19 as a model system...
2016: Molecular Vision
Sara Alonso-Álvarez, Maria Belén Vidriales, Maria Dolores Caballero, Oscar Blanco, Noemí Puig, Alejandro Martin, Maria Jesús Peñarrubia, Esther Zato, Josefina Galende, Abelardo Bárez, Miguel Alcoceba, Alberto Orfão, Marcos González, Ramón García-Sanz
Prognostic factors in Hodgkin lymphoma (HL) still fail to accurately identify high-risk patients. Tumor microenvironment in HL is a current focus of research for risk definition but few studies have focused on infiltrating lymphocytes. Here, we analyzed the number of tumor infiltrating lymphocytes by flow cytometry in diagnostic biopsies from 96 HL homogeneously treated patients with ABVD with or without radiotherapy. Most lymph node cells were lymphocytes (90 ± 17), with a median T/B/NK distribution of 74%/26%/0...
October 12, 2016: Leukemia & Lymphoma
Jingjing Wu, Cui Tang, Chunhua Yin
In order to reduce toxicity and improve antitumor therapeutic effects of doxorubicin (DOX) and recombinant human interleukin-2 (rhIL-2), we developed a hydrophilic cationic polymer (N,N,N-trimethyl chitosan, TMC) based nanocomplexes (FTCD/rhIL-2) which could efficiently mediate systemic co-delivery of hydrophobic DOX and water-soluble rhIL-2 to achieve the purpose of combination therapy. DOX was covalently conjugated to TMC through cis-aconitic anhydride (CA) which endowed nanocomplexes a pH-sensitive release of DOX, while rhIL-2 was loaded through electrostatic adsorption without compromise of bioactivity...
October 10, 2016: Acta Biomaterialia
Johan Lundberg, Emma Jussing, Zhenjiang Liu, Qingda Meng, Martin Rao, Erik Samén, Rikard Grankvist, Peter Damberg, Ernest Dodoo, Markus Maeurer, Staffan Holmin
Glioblastoma (GBM) is the most common and most severe form of malignant gliomas. The prognosis is poor with current combinations of pharmaceutical-, radio- and surgical therapy. A continuous search for new treatments has therefore been ongoing for many years. Therapy with tumor-infiltrating lymphocytes (TIL) is a clinically promising strategy to treat various cancers, including GBM. An endovascular intra-arterial injection of TIL as a method of delivery may, instead of intravenous infusion, result in better retention of effector cells within the tumor...
October 7, 2016: Cell Transplantation
Y Zhang, C Ma, M Wang, H Hou, L Cui, C Jiang, J Sun, X Qu
BACKGROUND: The role of the interaction between tumor cells and inflammatory cells in gallbladder carcinoma (GBC) is unclear. Inflammatory cells exist in both the tumor immune microenvironment and the host peripheral blood circulatory system. In the current study, we examined the prognostic value of inflammatory cells in the tumor microenvironment and peripheral blood in patients with GBC. METHODS: 98 patients with GBC were recruited in this retrospective study...
October 7, 2016: Clinical & Translational Oncology
Yukiyoshi Hirayama, Min Gi, Shotaro Yamano, Hirokazu Tachibana, Takahiro Okuno, Satoshi Tamada, Tatsuya Nakatani, Hideki Wanibuchi
Immunotherapy based on blockade of the programmed death-1 (PD-1)/programmed death-ligand 1(PD-L1) axis has shown promising clinical activity for renal cell carcinoma (RCC) patients; however, the most effective use of these agents in combination with conventional targeted therapy remains to be resolved. Here we evaluated the therapeutic efficacy of the combination of the mTOR inhibitor everolimus (EVE) and anti-PD-L1 using an immunocompetent mouse model of RCC. We first assessed the in vitro effect of EVE on PD-L1 expression in the human 786-O and mouse RENCA RCC cell lines and found that EVE up-regulated PD-L1 expression in these RCC cell lines...
October 6, 2016: Cancer Science
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