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tumor infiltrating lymphocytes

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
Ana M Contreras-Sandoval, María Merino, Marcos Vasquez, Iñaki F Trocóniz, Pedro Berraondo, María J Garrido
Blockade of PD-L1 with specific monoclonal antibodies (anti-PD-L1) represents a therapeutic strategy to increase the capability of the immune system to modulate the tumor immune-resistance. The relationship between anti-PD-L1 tumor exposition and anti-tumor effect represents a challenge that has been addressed in this work through the identification of certain biomarkers implicated in the antibody's mechanism of action, using a syngeneic melanoma mouse model. The development of an in-vitro/in-vivo platform has allowed us to investigate the PD-L1 behavior after its blockage with anti-PD-L1 at cellular level and in animals...
October 18, 2016: Oncotarget
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
Hamilton C Tsang, Susan Mathew, Cynthia M Magro
Diffuse large cell B-cell lymphoma of the skin is most commonly represented by diffuse large cell variants of primary cutaneous follicle center lymphoma and the leg-type lymphoma. In a minority of cases, the infiltrates are an expression of stage 4 disease of established extracutaneous B-cell lymphoma. We describe 1 female patient 85 years of age with an aggressive form of primary cutaneous B-cell lymphoma manifesting in multiple firm erythematous indurated solid nodules 1-2 cm each symmetrically on the face periorbitally and on the upper extremities bilaterally...
October 18, 2016: American Journal of Dermatopathology
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
Debasis Gochhait, Pranab Dey, Neelam Verma
BACKGROUND: Multiple myeloma or plasmacytoma resulting in malignant effusion is rarely described in literature. AIMS: In this paper, we have studied the seven rare cases of plasma cell infiltration in effusion fluid. MATERIALS AND METHODS: We studied six cases of pleural fluid and one case of ascetic fluid. Detailed cytological features, clinical history, bone marrow examinations, serum electrophoresis, and immunofixation data were analyzed...
July 2016: Journal of Cytology
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
Kirsten A M White, Li Luo, Todd A Thompson, Salina Torres, Chien-An Andy Hu, Nancy E Thomas, Jenna Lilyquist, Hoda Anton-Culver, Stephen B Gruber, Lynn From, Klaus J Busam, Irene Orlow, Peter A Kanetsky, Loraine D Marrett, Richard P Gallagher, Lidia Sacchetto, Stefano Rosso, Terence Dwyer, Anne E Cust, Colin B Begg, Marianne Berwick
Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0...
October 17, 2016: Cancer Medicine
Zhaohui Jin, Harry H Yoon
Preliminary clinical studies of anti-programmed cell death-1 (anti-PD-1) therapy in gastro-esophageal cancers have suggested promising single-agent activity. In patients who received prior treatment for advanced disease, pembrolizumab has been associated with a response rate of 20% in programmed cell death-1 ligand 1 (PD-L1)-positive tumors, and nivolumab with a response rate of 12% in unselected tumors. Both agents yielded a median duration of response lasting ~6-7 months. PD-L1 expression and microsatellite instability (MSI) have emerged as potential predictive markers for PD-1/PD-L1 blockade...
October 2016: Journal of Gastrointestinal Oncology
Manojkumar Bupathi, Christina Wu
Colorectal cancer (CRC) is a heterogeneous disease for which the treatment backbone has primarily been cytotoxic chemotherapy. With better understanding of the involved molecular mechanisms, it is now known that there are a number of epigenetic and genetic events, which are involved in CRC pathogenesis. Specific biomarkers have been identified which can be used to determine the clinical outcome of patients beyond tumor staging and predict for treatment efficacy. Molecular testing is now routinely performed to select for patients that will benefit the most from targeted agents and immunotherapy...
October 2016: Journal of Gastrointestinal Oncology
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
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
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