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CD155, cancer

Yaolin Xu, Guoyuan Cui, Zhongxiu Jiang, Ning Li, Xiaoye Zhang
Immune checkpoints expressed on tumor cells may suppress the cytotoxicity of tumor-infiltrating lymphocytes (TILs) via interaction with their ligands. In the present study, checkpoint proteins and ligands, including programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), cluster of differentiation (CD)155 and T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) were systematically analyzed in patients with small cell lung cancer (SCLC). Furthermore their clinicopathological features and survival rates were investigated...
March 2019: Oncology Letters
Maria Sofia Basile, Emanuela Mazzon, Andrea Russo, Santa Mammana, Antonio Longo, Vincenza Bonfiglio, Matteo Fallico, Rosario Caltabiano, Paolo Fagone, Ferdinando Nicoletti, Teresio Avitabile, Michele Reibaldi
Uveal melanoma (UM) is the most common primary intraocular cancer in adults. In the present study, we aimed to characterize the immunological features of primary UM cancer and to provide an association with prognostic markers and outcome. Also, we assessed the influence of the microenvironment on the expression of inhibitory immune checkpoints in UM. Genes of interest included MHC Class I and Class II molecules, as well as inhibitory immune-checkpoints, i.e. PDL1, PDL2, B7-H3, B7-H4, TBFRSF6B, CD47, CD155, GAL9, HVEM and CD200...
2019: PloS One
Ji Sung Kim, Boyeong Kim, Hong Kyung Lee, Hyung Sook Kim, Eun Jae Park, Yeo Jin Choi, Gi Beom Ahn, Jieun Yun, Jin Tae Hong, Youngsoo Kim, Sang-Bae Han
Natural killer (NK) cell killing of melanoma cells involves perforin-mediated delivery of granzymes from NK cells to cancer cells; however, how melanoma cells die remains poorly characterized. Here, we examined the dying process of melanoma cells by using time-lapse imaging. Upon contact with NK cells, B16-F10 cells rounded and most of them showed membrane rupture (98 min); however, B16 parent cells showed writhing and delayed membrane rupture (235 min). This morphological difference depended on the expression levels of myosin regulatory light chain 9 (MYL9) but not activating ligands (CD112, CD155, Rae-1, and MULT-1), SPI, FasL, or PD-L1...
December 21, 2018: International Immunopharmacology
Sareh Zhand, Seyed Masoud Hosseini, Alijan Tabarraei, Mohsen Saeidi, Marie Saghaeian Jazi, Mohamad Reza Kalani, Abdolvahab Moradi
Purpose: Colorectal cancer (CRC) is one of the most common causes of cancer death throughout the world. Replication-competent viruses, which are naturally able to infect and lyse tumor cells, seem to be promising in this field. The aim of this study was to evaluate the potential of oral poliovirus vaccine (OPV) on human CRC cells and elucidate the mechanism of apoptosis induction. Materials and methods: Protein and gene expression of poliovirus (PV) receptor (CD155) on four human CRC cell lines including HCT116, SW480, HT-29, and Caco-2 and normal fetal human colon (FHC) cell line as a control were examined by flow cytometry and SYBR Green Real-Time PCR, respectively...
2018: Oncolytic Virotherapy
Haoyu Sun, Qiang Huang, Mei Huang, Hao Wen, Renyong Lin, Meijuan Zheng, Kun Qu, Kun Li, Haiming Wei, Weihua Xiao, Rui Sun, Zhigang Tian, Cheng Sun
Immune checkpoint blockade has become a promising therapeutic approach to reverse immune cell exhaustion. Co-inhibitory CD96 and TIGIT, together with co-stimulatory CD226, bind to common ligand CD155. The balancing between three receptors fine tunes the immune responses against tumors. In this study, we investigated the expression of CD96, TIGIT and CD226 in 55 fresh human hepatocellular carcinoma (HCC) samples, 236 paraffin-embedded HCC samples, and 20 normal human livers. The cumulative percentage, absolute count, and MFI of CD96+ NK cells are significantly increased in the intratumoral tissues of HCC, and break the balance between three receptors...
November 8, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Huijun Zhao, Juan Ma, Ting Lei, Wanru Ma, Man Zhang
Expression of CD155 differs between tumor and normal tissues, and high expression of this molecule can promote tumor metastasis. Here, we investigate whether CD155 can serve as a target for T cell-mediated immunotherapy of human prostate cancer. We first demonstrate that prostate cancer cells, including PC-3, PC-3 M, and LNCAP cells, express CD155 at high levels. Next, the specific cytotoxic activity of activated T cells (ATCs) armed with a novel anti-CD3 × anti-CD155 bispecific antibody (CD155Bi-Ab) against tumor cells was evaluated by flow cytometry, lactate dehydrogenase assay (LDH), and ELISA...
October 29, 2018: Investigational New Drugs
Benjamin L Solomon, Ignacio Garrido-Laguna
Treatment strategies for patients with advanced solid tumors have traditionally been based on three different paradigms: surgery, cytotoxics (chemotherapy or radiation therapy) and targeted therapies. Immunotherapy has emerged as a novel treatment paradigm in our armamentarium. Unfortunately, most patients still do not benefit from immunotherapy. These patients often have "cold tumors" characterized by a paucity of effector T cells in the tumor microenvironment, low mutational load, low neoantigen burden and often an immunosuppressive tumor microenvironment...
November 2018: Cancer Immunology, Immunotherapy: CII
Jian Gao, Qianqian Zheng, Yue Shao, Wei Wang, Chenghai Zhao
CD155 has been implicated in migration, invasion, proliferation and apoptosis of human cancer cells, and DNA damage response caused by chemotherapeutic agents or reactive oxygen species has been shown to attribute to CD155 induction. Adriamycin (Adr) is one of the most common chemotherapeutic drugs used to treat breast cancer. Here we reported that treatment with Adr upregulated CD155 expression on several in vitro cultured breast cancer cells and in breast cancer cell 4T1 xenografts. We also found that CD155 knockdown or Adr treatment induced apoptosis of in vitro cultured cancer cells and cancer cells in 4T1 xenografts, and a combination of CD155 knockdown with Adr treatment induced more cell death than either of them...
October 2018: Apoptosis: An International Journal on Programmed Cell Death
Ross W Walton, Michael C Brown, Matthew T Sacco, Matthias Gromeier
We are pursuing cancer immunotherapy with a neuro-attenuated recombinant poliovirus, PVSRIPO. PVSRIPO is the live attenuated type 1 (Sabin) poliovirus vaccine carrying a heterologous internal ribosomal entry site (IRES) of human rhinovirus type 2 (HRV2). Intratumoral infusion of PVSRIPO is showing promise in the therapy of recurrent WHO grade IV malignant glioma (glioblastoma), a notoriously treatment-refractory cancer with dismal prognosis. PVSRIPO exhibits profound cytotoxicity in infected neoplastic cells expressing the poliovirus receptor CD155...
October 1, 2018: Journal of Virology
E O Ostapchuk, A Kali, N N Belyaev
We studied the role of cytokines TGF-β and TNFα in reduction of the cytolytic activity of NK cells towards tumor cells. Exogenous TGF-β and TNFα reduced the sensitivity of MiaPaCa2 pancreatic adenocarcinoma cells to NK cytotoxicity, which was associated with reduction of ULBP-1 expression and increase of HLA-E, HLA-G, CD155, and CD112 expression on Mia-PaCa2 cells. Changes in the expression of ligands for NK receptors on tumor cells induced by TGF-β and TNFα may contribute to reduction of cytotoxicity of tumor-associated NK cells and thus prevent an adequate antitumor immune response leading to the disease progress...
June 2018: Bulletin of Experimental Biology and Medicine
Hristo Georgiev, Inga Ravens, Georgia Papadogianni, Günter Bernhardt
CD96 represents a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily. CD96 is expressed mainly by cells of hematopoietic origin, in particular on T and NK cells. Upon interaction with CD155 present on target cells, CD96 was found to inhibit mouse NK cells, and absence of this interaction either by blocking with antibody or knockout of CD96 showed profound beneficial effects in containment of tumors and metastatic spread in murine model systems. However, our knowledge regarding CD96 functions remains fragmentary...
2018: Frontiers in Immunology
Vincenzo Bronte
The clinical benefits that have been achieved for a group of cancer patients with metastatic disease on checkpoint inhibitor therapy have kindled intense interest in understanding tumor-induced escape from T lymphocyte control. Other lymphoid cells also participate in tumor control; in particular, NK cells can limit hematogenous cancer metastasis spread and are also subject to negative regulation by developing cancers. In this issue of the JCI, Li and colleagues define an unanticipated role for the stress-induced protein CD155 in cancer metastasis...
June 1, 2018: Journal of Clinical Investigation
Baobiao Zhuo, Yuan Li, Feng Gu, Zhengwei Li, Qingzeng Sun, Yingchun Shi, Yang Shen, Fengfei Zhang, Rong Wang, Xiaodong Wang
The rapid development of metastatic lesions remains the leading cause of mortality for patients with osteosarcoma. CD155 serves a key role in cancer cell migration, invasion and metastasis. However, the function and mechanism of CD155 has not been explored in osteosarcoma metastasis. In the present study, we found that CD155 was significantly upregulated in lung metastatic tissue and the highly metastatic cell line K7M2-WT (K7M2) of osteosarcoma. Overexpression of CD155 in K7M2 cells enhanced lung metastasis, while inhibition of CD155 by an anti-CD155 monoclonal antibody reduced metastasis...
May 2018: Oncology Letters
Yuho Nakamura, Keisuke Naito, Yumi Yamashita-Kanemaru, Daisuke Komori, Rei Hirochika, Akira Shibuya, Kazuko Shibuya
T cell immunoglobulin and ITIM domains (TIGIT) is an inhibitory immunoreceptor expressed on NK cells, effector and memory T cells, and regulatory T cells (Tregs). The ligands for TIGIT are CD155 (PVR) and CD112 (PVRL2, nectin-2), which are broadly expressed on hematopoietic cells and nonhematopoietic cells. TIGIT negatively regulates antitumor responses, but promotes autoimmune reaction. Although neutralizing anti-human TIGIT mAbs are under clinical trials for cancers, how the blockade of TIGIT interaction with the ligands shows tumor immunity still remains unclear...
April 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
Jennifer Brooks, Bettina Fleischmann-Mundt, Norman Woller, Julia Niemann, Silvia Ribback, Kristin Peters, Ihsan Ekin Demir, Nina Armbrecht, Guralp O Ceyhan, Michael P Manns, Thomas C Wirth, Stefan Kubicka, Gunter Bernhardt, Mark J Smyth, Diego F Calvisi, Engin Gürlevik, Florian Kühnel
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and disseminating cancer resistant to therapy, including checkpoint immunotherapies, and early tumor resection and (neo)adjuvant chemotherapy fails to improve a poor prognosis. In a transgenic mouse model of resectable PDAC, we investigated the coordinated activation of T and natural killier (NK) cells in addition to gemcitabine chemotherapy to prevent tumor recurrence. Only neoadjuvant, but not adjuvant treatment with a PD-1 antagonist effectively supported chemotherapy and suppressed local tumor recurrence and improved survival involving both NK and T cells...
January 15, 2018: Cancer Research
Weiling He, Hui Zhang, Fei Han, Xinlin Chen, Run Lin, Wei Wang, Haibo Qiu, Zhenhong Zhuang, Qi Liao, Weijing Zhang, Qinbo Cai, Yongmei Cui, Wenting Jiang, Han Wang, Zunfu Ke
The T-cell surface molecule TIGIT is an immune checkpoint molecule that inhibits T-cell responses, but its roles in cancer are little understood. In this study, we evaluated the role TIGIT checkpoint plays in the development and progression of gastric cancer. We show that the percentage of CD8 T cells that are TIGIT+ was increased in gastric cancer patients compared with healthy individuals. These cells showed functional exhaustion with impaired activation, proliferation, cytokine production, and metabolism, all of which were rescued by glucose...
November 15, 2017: Cancer Research
Qianqian Zheng, Biao Wang, Jian Gao, Na Xin, Wei Wang, Xiaowen Song, Yue Shao, Chenghai Zhao
CD155, one of the nectin-like molecule family members, is involved in cell adhesion and motility. CD155 is overexpressed in several human cancers, but its role in proliferation and apoptosis of colorectal cancer remains unclear. We found that CD155 was up-regulated in colorectal cancer tissues. CD155 knockdown via shRNA lentiviruses inhibited colon cancers cell migration and invasion, with a reduction in the expression of FAK, Src and MMP-2. CD155 down-regulation also suppressed colon cancer cell proliferation, accompanied by changing expressions of some molecules related to cell cycle...
January 2018: Journal of Cellular and Molecular Medicine
Naomi Takahashi, Makoto Sugaya, Hiraku Suga, Tomonori Oka, Makiko Kawaguchi, Tomomitsu Miyagaki, Hideki Fujita, Takashi Inozume, Shinichi Sato
Immune checkpoint therapy, which targets regulatory pathways in T cells to enhance antitumor immune responses, has led to important clinical advances. CD155 is expressed in various types of cancer, and this surface molecule on tumor cells functions either as a co-stimulatory molecule or a co-inhibitory molecule, depending on its receptor. CD226, a CD155 ligand, is mainly expressed on natural killer cells and CD8+ T cells, playing important roles in natural killer cell-mediated cytotoxicity. In this study, we investigated the expression and function of CD155 and CD226 in cutaneous T-cell lymphoma (CTCL)...
August 2017: Journal of Investigative Dermatology
Elizabeth Denniston, Hannah Crewdson, Nicole Rucinsky, Andrew Stegman, Diana Remenar, Katherine Moio, Brianne Clark, Alexandra Higginbotham, Ross Keffer, Sarah Brammer, Joseph Horzempa
The inauguration of novel treatment strategies into the clinical setting faces a number of hurdles. In addition to treatment efficacy and safety, acceptance by doctors and patients is paramount to the success of novel therapies. Although viruses are the cause of numerous infectious diseases, these acellular entities have been harnessed over the years to benefit mankind. Recently, a recombinant Poliovirus-Rhinovirus Chimera (PVSRIPO) has shown promise for the treatment of glioblastoma in clinical trials as well as other cancer types in animal models...
2016: American Journal of Virology
Fabrizio Antonangeli, Alessandra Soriani, Biancamaria Ricci, Andrea Ponzetta, Giorgia Benigni, Stefania Morrone, Giovanni Bernardini, Angela Santoni
Recognition of tumor cells by the immune system is a key step in cancer eradication. Melphalan is an alkylating agent routinely used in the treatment of patients with multiple myeloma (MM), but at therapeutic doses it leads to an immunosuppressive state due to lymphopenia. Here, we used a mouse model of MM to investigate the ability of in vivo treatment with low doses of melphalan to modulate natural killer (NK) cell activity, which have been shown to play a major role in the control of MM growth. Melphalan treatment was able to enhance the surface expression of the stress-induced NKG2D ligands RAE-1 and MULT-1, and of the DNAM-1 ligand PVR (CD155) on MM cells, leading to better tumor cell recognition and killing by NK cells, as highlighted by NK cell increased degranulation triggered by melphalan-treated tumor cells...
2016: Oncoimmunology
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