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Cancer Immunology Research

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https://www.readbyqxmd.com/read/29921599/experimental-lung-metastases-in-mice-are-more-effectively-inhibited-by-blockade-of-il23r-than-il23
#1
Juming Yan, Stacey Allen, Dipti Vijayan, Xian-Yang Li, Heidi Harjunpää, Kazuyoshi Takeda, Jing Liu, Daniel J Cua, Mark J Smyth, Michele W L Teng
Tumor-induced immunosuppression is mediated through various mechanisms including engagement of immune checkpoint receptors on effector cells, function of immunoregulatory cells such as Tregs and MDSCs, and deployment of immunosuppressive cytokines such as TGFβ and IL10. IL23 is a cytokine that negatively affects antitumor immunity. In this study, we investigated whether IL23-deficient (IL23p19-/-) and IL23R-deficient (IL23R-/-) mice phenocopied each other, with respect to their tumor control. We found that IL23R-/- mice had significantly fewer lung metastases compared to IL23p19-/- mice across three different experimental lung metastasis models (B16F10, LWT1, RM-1)...
June 19, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29915023/enhancement-of-peptide-vaccine-immunogenicity-by-increasing-lymphatic-drainage-and-boosting-serum-stability
#2
Kelly D Moynihan, Rebecca L Holden, Naveen K Mehta, Chensu Wang, Mark R Karver, Jens Dinter, Simon Liang, Wuhbet Abraham, Mariane B Melo, Angela Q Zhang, Na Li, Sylvie Le Gall, Bradley Pentelute, Darrell J Irvine
Antitumor T-cell responses have the potential to be curative in cancer patients, but the induction of potent T-cell immunity through vaccination remains a largely unmet goal of immunotherapy. We previously reported that the immunogenicity of peptide vaccines could be increased by maximizing delivery to lymph nodes (LNs), where T-cell responses are generated. This was achieved by conjugating the peptide to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG (DSPE-PEG) to promote albumin binding, which resulted in enhanced lymphatic drainage and improved T-cell responses...
June 18, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29915022/enhanced-cancer-immunotherapy-with-smad3-slilencing-nk-92-cells
#3
Qing Ming Wang, Patrick Ming-Kuen Tang, Guang-Yu Lian, Chunjie Li, Jinghong Li, Xiao-Ru Huang, Ka-Fai To, Hui-Yao Lan
Natural killer (NK) cells, early effectors in anti-cancer immunity, are paralyzed by TGF-β1, an immunosuppressive cytokine produced by cancer cells. Development and activity of NK cells are largely inhibited in the Smad3-dependent tumor microenvironment. Here, we used genetic engineering to generate a stable SMAD3-silencing human NK cell line NK-92-S3KD, whose cancer-killing activity and cytokine production were significantly enhanced under TGF-β1-rich condition compared to the parental cell line. Interestingly, we identified that IFNG gene is a direct E4BP4 target gene...
June 18, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29907693/exosomes-shuttle-trex1-sensitive-ifn-stimulatory-dsdna-from-irradiated-cancer-cells-to-dendritic-cells
#4
Julie M Diamond, Claire Vanpouille-Box, Sheila Spada, Nils-Petter Rudqvist, Jessica Chapman, Beatrix Ueberheide, Karsten A Pilones, Yasmeen Sarfraz, Silvia C Formenti, Sandra Demaria
Radiotherapy (RT) used at immunogenic doses leads to accumulation of cytosolic double-stranded DNA (dsDNA) in cancer cells, which activates type I IFN (IFN-I) via the cGAS/STING pathway. Cancer cell-derived IFN-I is required to recruit BATF3-dependent dendritic cells (DCs) to poorly immunogenic tumors and trigger antitumor T-cell responses in combination with immune checkpoint blockade. We have previously demonstrated that the exonuclease TREX1 regulates radiation immunogenicity by degrading cytosolic dsDNA...
June 15, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29895574/primary-t-cells-from-cutaneous-t-cell-lymphoma-skin-explants-display-an-exhausted-immune-checkpoint-profile
#5
Christiane Querfeld, Samantha Leung, Patricia L Myskowski, Shane A Curran, Debra A Goldman, Glenn Heller, Xiwei Wu, Sung Hee Kil, Sneh Sharma, Kathleen J Finn, Steven Horwitz, Alison Moskowitz, Babak Mehrara, Steven T Rosen, Allan C Halpern, James W Young
Cutaneous T-cell lymphoma (CTCL) develops from clonally expanded CD4+ T cells in a background of chronic inflammation. Although dendritic cells (DCs) stimulate T cells and are present in skin, cutaneous T cells in CTCL do not respond with effective antitumor immunity. We evaluated primary T-cell and DC émigrés from epidermal and dermal explant cultures of skin biopsies from CTCL patients (n = 37) and healthy donors (n = 5). Compared with healthy skin, CD4+ CTCL populations contained more T cells expressing PD-1, CTLA-4, and LAG-3...
June 12, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29895573/the-mutation-associated-neoantigen-functional-expansion-of-specific-t-cells-manafest-assay-a-sensitive-platform-for-monitoring-antitumor-immunity
#6
Ludmila Danilova, Valsamo Anagnostou, Justina X Caushi, John-William Sidhom, Haidan Guo, Hok Yee Chan, Prerna Suri, Ada J Tam, Jiajia Zhang, Margueritta El Asmar, Kristen A Marrone, Jarushka Naidoo, Julie R Brahmer, Patrick M Forde, Alexander S Baras, Leslie Cope, Victor E Velculescu, Drew Pardoll, Franck Housseau, Kellie N Smith
Mutation-associated neoantigens (MANAs) are a target of antitumor T-cell immunity. Sensitive, simple, and standardized assays are needed to assess the repertoire of functional MANA-specific T cells in oncology. Assays analyzing in vitro cytokine production such as ELISpot and intracellular cytokine staining (ICS) have been useful but have limited sensitivity in assessing tumor-specific T-cell responses and do not analyze antigen-specific T-cell repertoires. The FEST (Functional Expansion of Specific T cells) assay described herein integrates TCR sequencing of short-term, peptide-stimulated cultures with a bioinformatic platform to identify antigen-specific clonotypic amplifications...
June 12, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29871885/pd-l1-binds-to-b7-1-only-in-cis-on-the-same-cell-surface
#7
Apoorvi Chaudhri, Yanping Xiao, Alyssa N Klee, Xiaoxu Wang, Baogong Zhu, Gordon J Freeman
Programmed death ligand 1 (PD-L1)-mediated immune suppression regulates peripheral tolerance and is often co-opted by tumors to evade immune attack. PD-L1 binds to PD-1 but also binds to B7-1 (CD80) to regulate T-cell function. Binding interactions of PD-L1 with B7-1 and its functional role need further investigation to understand differences between PD-1 and PD-L1 tumor immunotherapy. We examined the molecular orientation of PD-L1 binding to B7-1 using cell-to-cell binding assays, ELISA, and flow cytometry...
June 5, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29792298/nanobody-antigen-conjugates-elicit-hpv-specific-anti-tumor-immune-responses
#8
Andrew W Woodham, Ross W Cheloha, Jingjing Ling, Mohammad Rashidian, Stephen C Kolifrath, Maia Mesyngier, Joao N Duarte, Justin M Bader, Joseph G Skeate, Diane M Da Silva, W Martin Kast, Hidde L Ploegh
High-risk human papillomavirus-associated cancers express viral oncoproteins (e.g., E6 and E7) that induce and maintain the malignant phenotype. The viral origin of these proteins makes them attractive targets for development of a therapeutic vaccine. Camelid-derived single-domain antibody fragments (nanobodies or VHHs) that recognize cell surface proteins on antigen-presenting cells (APCs) can serve as targeted delivery vehicles for antigens attached to them. Such VHHs were shown to induce CD4+ and CD8+ T-cell responses against model antigens conjugated to them via sortase, but antitumor responses had not yet been investigated...
May 23, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29784636/adaptive-nk-cells-resist-regulatory-t-cell-suppression-driven-by-il-37
#9
Dhifaf Sarhan, Keli L Hippen, Amanda Lemire, Skyler Hying, Xianghua Luo, Todd Lenvik, Julie Curtsinger, Zachary Davis, Bin Zhang, Sarah Cooley, Frank Cichocki, Bruce R Blazar, Jeffrey S Miller
Natural Killer (NK) cells are capable of fighting viral infections and cancer. However, these responses are inhibited by immune suppressor cells in the tumor microenvironment. Tumor progression promotes the recruitment and generation of intratumoral regulatory T cells (Tregs), associated with a poor prognosis in cancer patients. Here, we show that canonical NK cells are highly susceptible to Treg-mediated suppression, in contrast to highly resistant CD57+ FcεRγ-NKG2C+ adaptive (CD56+CD3-) NK cells that expand in cytomegalovirus (CMV)-exposed individuals...
May 21, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29769244/a-cs1-nkg2d-bispecific-antibody-collectively-activates-cytolytic-immune-cells-against-multiple-myeloma
#10
Wing Keung Chan, Siwen Kang, Youssef Youssef, Erin N Glankler, Emma R Barrett, Alex M Carter, Elshafa H Ahmed, Aman Prasad, Luxi Chen, Jianying Zhang, Don M Benson, Michael A Caligiuri, Jianhua Yu
Multiple myeloma (MM) is an incurable hematological malignancy of plasma cells with an estimated 30,000 new cases diagnosed each year in the United States, signifying the need for new therapeutic approaches. We hypothesized that targeting MM using a bispecific antibody (biAb) to simultaneously engage both innate and adaptive cytolytic immune cells could present potent antitumor activity. We engineered a biAb by fusing an anti-CS1 single chain variable fragment (scFv) and an anti-NKG2D scFv (CS1-NKG2D biAb)...
May 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29764837/il22-promotes-kras-mutant-lung-cancer-by-induction-of-a-pro-tumor-immune-response-and-protection-of-stemness-properties
#11
Nasim Khosravi, Mauricio S Caetano, Amber M Cumpian, Nese Unver, Cynthia De la Garza Ramos, Oscar Noble, Soudabeh Daliri, Belinda J Hernandez, Berenice A Gutierrez, Scott E Evans, Samir Hanash, Andrei M Alekseev, Yi Yang, Seon Hee Chang, Roza Nurieva, Humam Kadara, Jichao Chen, Edwin J Ostrin, Seyed Javad Moghaddam
Somatic KRAS mutations are the most common oncogenic variants in lung cancer and are associated with poor prognosis. Using a Kras-induced lung cancer mouse model, CC-LR, we previously showed a role for inflammation in lung tumorigenesis through activation of the NF-kB pathway, along with induction of interleukin 6 (IL6) and an IL17-producing CD4+ T-helper cell response. IL22 is an effector molecule secreted by CD4+ and γδ T cells that we previously found to be expressed in CC-LR mice. IL22 mostly signals through the STAT3 pathway and is thought to act exclusively on non-hematopoietic cells with basal IL22 receptor (IL22R) expression on epithelial cells...
May 15, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29764836/subcellular-localization-of-antigen-dictates-delivery-of-cd4-t-cell-help-for-the-ctl-response-upon-therapeutic-dna-vaccination-into-the-skin
#12
Nikolina Bąbała, Astrid Bovens, Evert de Vries, Victoria Iglesias-Guimarais, Tomasz Ahrends, Matthew F Krummel, Jannie Borst, Adriaan D Bins
In a mouse model of therapeutic DNA vaccination, we studied how the subcellular localization of vaccine protein impacts antigen delivery to professional antigen presenting cells (pAPCs) and efficiency of CTL priming. Cytosolic, membrane-bound, nuclear, and secretory versions of ZsGreen fluorescent protein, conjugated to MHC class I and -II ovalbumin (OVA) epitopes were expressed in keratinocytes by DNA vaccination into the skin. ZsGreen-OVA versions reached B cells in the skin-draining lymph node (dLN) that proved irrelevant for CTL priming...
May 15, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29748391/tumor-specific-inhibition-of-in-situ-vaccination-by-distant-untreated-tumor-sites
#13
Zachary S Morris, Emily I Guy, Lauryn R Werner, Peter M Carlson, Clinton M Heinze, Jasdeep S Kler, Sara M Busche, Abigail A Jaquish, Raghava N Sriramaneni, Lakeesha Carmichael, Hans Loibner, Stephen D Gillies, Alan J Korman, Amy K Erbe, Jacquelyn A Hank, Alexander L Rakhmilevich, Paul M Harari, Paul M Sondel
In situ vaccination is an emerging cancer treatment strategy that uses local therapies to stimulate a systemic antitumor immune response. We previously reported an in situ vaccination effect when combining radiation (RT) with intra-tumor (IT) injection of tumor-specific immunocytokine (IC), a fusion of tumor-specific antibody and IL2 cytokine. In mice bearing two tumors, we initially hypothesized that delivering RT plus IT-IC to the "primary" tumor would induce a systemic antitumor response causing regression of the "secondary" tumor...
May 10, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29748390/the-clinical-activity-of-pd-1-pd-l1-inhibitors-in-metastatic-non-clear-cell-renal-cell-carcinoma
#14
Rana R McKay, Dominick Bossé, Wanling Xie, Stephanie A M Wankowicz, Abdallah Flaifel, Raphael Brandao, Aly-Khan Lalani, Dylan J Martini, Xiao X Wei, David A Braun, Eliezer M Van Allen, Daniel Castellano, Guillermo de Velasco, J Connor Wells, Daniel Y C Heng, Andre P Fay, Fabio A Schutz, JoAnn Hsu, Sumanta Kumar Pal, Jae-Lyun Lee, James Hsieh, Lauren C Harshman, Sabina Signoretti, Robert J Motzer, Darren R Feldman, Toni K Choueiri
Programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors have shown activity in metastatic clear cell renal cell carcinoma (ccRCC). Data on the activity of these agents in patients with non-clear cell RCC (nccRCC) or patients with sarcomatoid/rhabdoid differentiation is limited. In this multicenter analysis, we explored the efficacy of PD-1/PD-L1 inhibitors in patients with nccRCC or sarcomatoid/rhabdoid differentiation. Baseline and follow-up demographic, clinical, treatment, and radiographic data were collected...
May 10, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29720381/whole-exome-and-transcriptome-analyses-integrated-with-microenvironmental-immune-signatures-of-lung-squamous-cell-carcinoma
#15
Jeong-Sun Seo, Ji Won Lee, Ahreum Kim, Jong-Yeon Shin, Yoo Jin Jung, Sae Bom Lee, Yoon Ho Kim, Samina Park, Hyun Joo Lee, In-Kyu Park, Chang Hyun Kang, Ji-Young Yun, Jihye Kim, Young T Kim
The immune microenvironment in lung squamous cell carcinoma (LUSC) is not well understood, with interactions between the host immune system and the tumor, as well as the molecular pathogenesis of LUSC, awaiting better characterization. To date, no molecularly targeted agents have been developed for LUSC treatment. Identification of predictive and prognostic biomarkers for LUSC could help optimize therapy decisions. We sequenced whole exomes and RNA from 101 tumors and matched noncancer control Korean samples...
May 2, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29720380/car-t-cells-surface-engineered-with-drug-encapsulated-nanoparticles-can-ameliorate-intratumoral-t-cell-hypofunction
#16
Natnaree Siriwon, Yu Jeong Kim, Elizabeth Louise Siegler, Xianhui Chen, Jennifer A Rohrs, Yarong Liu, Pin Wang
One limiting factor of CAR T-cell therapy for treatment of solid cancers is the suppressive tumor microenvironment, which inactivates the function of tumor infiltrating lymphocytes (TILs) through the production of immunosuppressive molecules such as adenosine. Adenosine inhibits the function of CD4+ and CD8+ T cells by binding to and activating the A2a adenosine receptor (A2aR) expressed on their surface. This suppression pathway can be blocked using the A2aR-specific small molecule antagonist SCH-58261 (SCH), but its applications have been limited owing to difficulties delivering this drug to immune cells within the tumor microenvironment (TME)...
May 2, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29691234/drug-induced-senescent-multiple-myeloma-cells-elicit-nk-cell-proliferation-by-direct-or-exosome-mediated-il15-trans-presentation
#17
Cristiana Borrelli, Biancamaria Ricci, Elisabetta Vulpis, Cinzia Fionda, Maria Rosaria Ricciardi, Maria Teresa Petrucci, Laura Masuelli, Agnese Peri, Marco Cippitelli, Alessandra Zingoni, Angela Santoni, Alessandra Soriani
Treatment of multiple myeloma (MM) cells with sublethal doses of genotoxic drugs leads to senescence and results in increased NK cell recognition and effector functions. Herein, we demonstrated that doxorubicin- and melphalan-treated senescent cells display increased expression of IL15, a cytokine involved in NK cell activation, proliferation, and maturation. IL15 upregulation was evident at the mRNA and protein level, both in MM cell lines and malignant plasma cells from patients' bone marrow (BM) aspirates...
April 24, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29678874/mitochondrial-morphological-and-functional-reprogramming-following-cd137-4-1bb-co-stimulation
#18
Alvaro Teijeira, Sara Labiano, Saray Garasa, Inaki Etxeberria, Eva Santamaria, Ana Rouzaut, Michel Enamorado, Arantza Azpilikueta, Susana Inoges, Elixabet Bolanos-Mateo, Maria Angela Aznar, Alfonso R Sanchez-Paulete, David Sancho, Ignacio Melero
T and NK lymphocytes express CD137 (4-1BB), a costimulatory receptor of the TNFR family whose function is exploitable for cancer immunotherapy. Mitochondria regulate the function and survival of T lymphocytes. Herein, we show that CD137 costimulation provided by agonist mAb and CD137L (4-1BBL) induced mitochondria enlargement that resulted in enhanced mitochondrial mass and transmembrane potential in human and mouse CD8+ T cells. Such mitochondrial changes increased T-cell respiratory capacities and were critically dependent on mitochondrial fusion protein OPA-1 expression...
April 20, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29858188/literature-round-up-impactful-published-papers-article-recommendations-from-our-deputy-and-senior-editors
#19
(no author information available yet)
No abstract text is available yet for this article.
June 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29700053/tk-inhibitor-pazopanib-primes-dcs-by-downregulation-of-the-%C3%AE-catenin-pathway
#20
Ilaria Grazia Zizzari, Chiara Napoletano, Andrea Botticelli, Salvatore Caponnetto, Fabio Calabrò, Alain Gelibter, Aurelia Rughetti, Ilary Ruscito, Hassan Rahimi, Ernesto Rossi, Giovanni Schinzari, Paolo Marchetti, Marianna Nuti
Tyrosine kinase inhibitors (TKIs) target angiogenesis by affecting, for example, the VEGF receptors in tumors and have improved outcomes for patients with metastatic renal cell carcinoma (mRCC). Immune checkpoint inhibitors (ICIs) have also been proposed for treatment of mRCC with encouraging results. A better understanding of the activity of immune cells in mRCC, the immunomodulatory effects of TKIs, and the characteristics defining patients most likely to benefit from various therapies will help optimize immunotherapeutic approaches...
June 2018: Cancer Immunology Research
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