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Cancer Immunology Research

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https://www.readbyqxmd.com/read/28970196/stereotactic-radiotherapy-increases-functionally-suppressive-regulatory-t-cells-in-the-tumor-microenvironment
#1
Yuki Muroyama, Thomas R Nirschl, Christina M Kochel, Zoila Lopez-Bujanda, Debebe Theodros, Wendy Mao, Maria A Carrera-Haro, Ali Ghasemzadeh, Ariel E Marciscano, Esteban Velarde, Ada J Tam, Christopher J Thoburn, Muniza Uddin, Alan K Meeker, Robert A Anders, Drew M Pardoll, Charles G Drake
Radiotherapy (RT) enhances innate and adaptive antitumor immunity; however, the effects of radiation on suppressive immune cells, such as regulatory T cells (Tregs), in the tumor microenvironment (TME) are not fully elucidated. Although previous reports suggest an increased Treg infiltration after radiation, whether these Tregs are functionally suppressive remains undetermined. To test the hypothesis that RT enhances the suppressive function of Treg in the TME, we selectively irradiated implanted tumors using the Small Animal Radiation Research Platform (SARRP), which models stereotactic radiotherapy in human patients...
October 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28963140/increasing-tumor-infiltrating-t-cells-through-inhibition-of-cxcl12-with-nox-a12-synergizes-with-pd-1-blockade
#2
Dirk Zboralski, Kai Hoehlig, Dirk Eulberg, Anna Froemming, Axel Vater
Immune checkpoint inhibitors promote T cell-mediated killing of cancer cells, however only a subset of patients benefit from the treatment. A possible reason for this limitation may be that the tumor microenvironment (TME) is immune privileged, which may exclude cytotoxic T cells from the vicinity of cancer cells. The chemokine CXCL12 is key to the TME-driven immune suppression. In this study we investigated the potential of CXCL12 inhibition by use of the clinical-stage L-RNA-aptamer NOX-A12 (olaptesed pegol) to increase the number of tumor-infiltrating lymphocytes...
September 28, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28963139/pi3kgamma-activates-integrin-alpha4-and-promotes-immune-suppressive-myeloid-cell-polarization-during-tumor-progression
#3
Judith A Varner, Philippe Foubert, Megan M Kaneda
Immunosuppressive myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) accumulate in tumors where they inhibit T cell-mediated antitumor immune responses and promote tumor progression. Myeloid cell PI3Kgamma plays a role in regulating tumor immune suppression by promoting integrin alpha4-dependent MDSC recruitment to tumors and by stimulating the immunosuppressive polarization of MDSCs and TAMs. Here we show that integrin alpha4 promotes immunosuppressive polarization of MDSCs and TAMs downstream of PI3Kγ, thereby inhibiting antitumor immunity...
September 28, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28947544/treg-depletion-licenses-t-cell-driven-hev-neogenesis-and-promotes-tumor-destruction
#4
Emily J Colbeck, Emma Jones, James P Hindley, Kathryn Smart, Ralph Schulz, Molly Browne, Scott Cutting, Anwen Williams, Lee Parry, Andrew Godkin, Carl F Ware, Ann Ager, Awen Gallimore
T-cell infiltration into tumors represents a critical bottleneck for immune-mediated control of cancer. We previously showed that this bottleneck can be overcome by depleting immunosuppressive Foxp3+ regulatory T cells (Tregs), a process which can increase frequencies of tumor-infiltrating lymphocytes (TILs) through promoting development of specialized portals for lymphocyte entry, namely high endothelial venules (HEVs). In this paper, we used a carcinogen-induced tumor model, that allows for co-evolution of the tumor microenvironment and the immune response, to demonstrate that Treg depletion not only results in widespread disruption to HEV networks in lymph nodes (LNs) but activates CD8+ T cells, which then drive intratumoral HEV development...
September 25, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28935649/melanoma-sequentially-suppresses-different-dc-subsets-in-the-sentinel-lymph-node-affecting-disease-spread-and-recurrence
#5
Mari F C M van den Hout, Bas D Koster, Berbel J R Sluijter, Barbara G Molenkamp, Rieneke van de Ven, Alfons J M van den Eertwegh, Rik J Scheper, Paul A van Leeuwen, M Petrousjka van den Tol, Tanja D de Gruijl
Melanoma exerts immune suppressive effects to facilitate tumor progression and metastatic spread. We studied these effects on dendritic cell (DC) and T-cell subsets in 36 melanoma sentinel lymph nodes (SLN) from 28 stage I-III melanoma patients and determined their clinical significance. Four conventional DC subsets; plasmacytoid DCs; and CD4+, CD8+, and regulatory T cells (Tregs) were analyzed by flow cytometry. We correlated these data to clinical parameters and determined their effect on local and distant melanoma recurrence, with a median follow-up of 75 months...
September 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28924054/immunosurveillance-and-immunoediting-of-breast-cancer-via-class-i-mhc-receptors
#6
Megan M Tu, Mir Munir A Rahim, Céline Sayed, Ahmad Bakur Mahmoud, Andrew P Makrigiannis
Ly49 receptors, which recognize "self" class I major histocompatibility complex (MHC-I) molecules, enable natural killer (NK) cells to detect loss of MHC-I expression on transformed and virally infected cells. The impact of NK cell-mediated MHC-I surveillance on immunoediting of breast cancer is still not fully understood. This work assesses the impact of Ly49 receptors on tumor development in terms of cancer control and in driving immune-evading cancer mutations. Genetically modified Ly49-deficient mice and those lacking NK cells through antibody depletion were less able to control E0771-derived mammary tumors in an MHC-I-dependent fashion...
September 18, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28874354/the-inhibitory-signaling-receptor-protocadherin-18-regulates-tumor-infiltrating-cd8-t-cell-function
#7
Alan B Frey
Cancers are infiltrated with antitumor CD8(+) T cells that arise during tumor growth, but are defective in effector phase functions because of the suppressive microenvironment. The reactivation of TILs can result in tumor destruction, showing that lytic dysfunction in CD8(+) tumor-infiltrating lymphocytes (TIL) permits tumor growth. Like all memory T cells, TILs express inhibitory signaling receptors (aka checkpoint inhibitor molecules) that downregulate TCR-mediated signal transduction upon TIL interaction with cells expressing cognate ligands, thereby restricting cell activation and preventing the effector phase...
September 5, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28851692/photodynamic-immune-checkpoint-therapy-eradicates-local-and-distant-tumors-by-cd8-t-cells
#8
Jan Willem Kleinovink, Marieke F Fransen, Clemens W Löwik, Ferry Ossendorp
Photodynamic therapy (PDT) is a clinically applied tumor ablation method that reduces tumor burden and may induce T-cell responses, providing a therapeutic option for mutated tumors. In this study, we applied PDT in two mouse tumor models and assessed its effect on outgrowth of PDT-treated and distant untreated tumors. PDT of established tumors resulted in complete tumor eradication in most mice, which were then protected against tumor rechallenge. Correspondingly, the therapeutic effect was abrogated upon systemic depletion of CD8(+) T cells, indicating PDT-induced tumor antigen cross-presentation and T-cell activation...
August 29, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28848054/neoadjuvant-interferons-critical-for-effective-pd-1-based-immunotherapy-in-tnbc
#9
Natasha K Brockwell, Katie L Owen, Damien Zanker, Alex Spurling, Jai Rautela, Hendrika M Duivenvoorden, Nikola Baschuk, Franco Caramia, Sherene Loi, Phillip K Darcy, Elgene Lim, Belinda S Parker
The lack of targeted therapies available for triple-negative breast cancer (TNBC) patients who fail to respond to first-line chemotherapy has sparked interest in immunotherapeutic approaches. However, trials utilizing checkpoint inhibitors targeting the PD-1/PD-L1 axis in TNBC have had underwhelming responses. Here, we investigated the interplay between type I IFN signaling and the PD-1/PD-L1 axis and tested the impact of combining IFN inducers, as immune activators, with anti-PD-1, to induce an antimetastatic immune response...
August 28, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28848053/antigen-presenting-intratumoral-b-cells-affect-cd4-til-phenotypes-in-non-small-cell-lung-cancer-patients
#10
Tullia C Bruno, Peggy J Ebner, Brandon L Moore, Olivia G Squalls, Katherine A Waugh, Evgeniy B Eruslanov, Sunil Singhal, John D Mitchell, Wilbur A Franklin, Daniel T Merrick, Martin D McCarter, Brent E Palmer, Jeffrey A Kern, Jill E Slansky
Effective immunotherapy options for patients with non-small cell lung cancer (NSCLC) are becoming increasingly available. The immunotherapy focus has been on tumor-infiltrating T cells (TILs); however, tumor-infiltrating B cells (TIL-Bs) have also been reported to correlate with NSCLC patient survival. The function of TIL-Bs in human cancer has been understudied, with little focus on their role as antigen-presenting cells and their influence on CD4(+) TILs. Compared with other immune subsets detected in freshly isolated primary tumors from NSCLC patients, we observed increased numbers of intratumoral B cells relative to B cells from tumor-adjacent tissues...
August 28, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28842470/il15-infusion-of-cancer-patients-expands-the-subpopulation-of-cytotoxic-cd56-bright-nk-cells-and-increases-nk-cell-cytokine-release-capabilities
#11
Sigrid Dubois, Kevin C Conlon, Jürgen R Müller, Jennifer Hsu-Albert, Nancy Beltran, Bonita R Bryant, Thomas A Waldmann
The cytokine IL15 is required for survival and activation of natural killer (NK) cells as well as expansion of NK-cell populations. Here, we compare the effects of continuous IL15 infusions on NK-cell subpopulations in cancer patients. Infusions affected the CD56(bright) NK-cell subpopulation in that the expansion rates exceeded those of CD56(dim) NK-cell populations with a 350-fold increase in their total cell numbers compared with 20-fold expansion for the CD56(dim) subset. CD56(bright) NK cells responded with increased cytokine release to various stimuli, as expected given their immunoregulatory functions...
August 25, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28835422/tumor-associated-macrophages-promote-epigenetic-silencing-of-gelsolin-through-dna-methyltransferase-1-in-gastric-cancer-cells
#12
Hao-Chen Wang, Chin-Wang Chen, Chia-Lung Yang, I-Min Tsai, Ya-Chin Hou, Chang-Jung Chen, Yan-Shen Shan
Epigenetic repression of the tumor suppressor gelsolin (GSN) is frequently observed in cancers. Chronic inflammation can promote tumor progression via aberrant DNA methylation. In this study, we investigated the role of tumor-associated macrophages (TAMs) in DNA methylation of the GSN gene during gastric cancer progression. Immunofluorescence staining of 121 gastric cancer tissues showed aberrant localization of GSN and DNA methyltransferase 1 (DNMT1) and juxtaposition of DNMT1 and M2 TAMs. Decreased GSN protein and mRNA expression and increased DNA methylation in the GSN promoter were observed in gastric cancer cell lines and clinical specimens...
August 23, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28811289/primary-tumors-limit-metastasis-formation-through-induction-of-il15-mediated-crosstalk-between-patrolling-monocytes-and-nk-cells
#13
Hiroshi Kubo, Sofia Mensurado, Natacha Goncalves-Sousa, Karine Serre, Bruno Silva-Santos
Metastases are responsible for the vast majority of cancer-related deaths. Although tumor cells can become invasive early during cancer progression, metastases formation typically occurs as a late event. How the immune response to primary tumors may dictate this outcome remains poorly understood, which hampers our capacity to manipulate it therapeutically. Here we used a two-step experimental model, based on the highly aggressive B16F10 melanoma, that temporally segregates the establishment of primary tumors (subcutaneously) and the formation of lung metastases (from intravenous injection)...
August 15, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28778961/using-antigen-specific-b-cells-to-combine-antibody-and-t-cell-based-cancer-immunotherapy
#14
Kerstin Wennhold, Martin Thelen, Hans Anton Schlößer, Natalie Haustein, Sabrina Reuter, Maria Garcia-Marquez, Axel Lechner, Sebastian Kobold, Felicitas Rataj, Olaf Utermöhlen, Geothy Chakupurakal, Sebastian Theurich, Michael Hallek, Hinrich Abken, Alexander Shimabukuro-Vornhagen, Michael von Bergwelt-Baildon
Cancer immunotherapy by therapeutic activation of T cells has demonstrated clinical potential. Approaches include checkpoint inhibitors and chimeric antigen receptor T cells. Here, we report the development of an alternative strategy for cellular immunotherapy that combines induction of a tumor-directed T-cell response and antibody secretion without the need for genetic engineering. CD40 ligand stimulation of murine tumor antigen-specific B cells, isolated by antigen-biotin tetramers, resulted in the development of an antigen-presenting phenotype and the induction of a tumor antigen-specific T-cell response...
August 4, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28775209/role-for-high-affinity-ige-receptor-in-prognosis-of-lung-adenocarcinoma-patients
#15
Dalam Ly, Chang-Qi Zhu, Michael Cabanero, Ming-Sound Tsao, Li Zhang
Cancer development and biology is influenced by the host immune system. Emerging data indicate that the context of immune cell infiltrates may contribute to cancer prognosis. However, the types of infiltrating immune cells that are critical for cancer development remain controversial. In attempts to gain insights into the immune networks that regulate and/or predict tumor progression, gene expression analysis was conducted on microarray datasets of resected tumor samples from 128 early-stage non-small cell lung cancer (NSCLC) adenocarcinoma patients...
August 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28760732/role-of-nox2-derived-reactive-oxygen-species-in-nk-cell-mediated-control-of-murine-melanoma-metastasis
#16
Ebru Aydin, Junko Johansson, Faisal Hayat Nazir, Kristoffer Hellstrand, Anna Martner
The NADPH oxidase of myeloid cells, NOX2, generates reactive oxygen species (ROS) to eliminate pathogens and malignant cells. NOX2-derived ROS have also been proposed to dampen functions of natural killer (NK) cells and other antineoplastic lymphocytes in the microenvironment of established tumors. The mechanisms by which NOX2 and ROS influence the process of distant metastasis have only been partially explored. Here, we utilized genetically NOX2-deficient mice and pharmacologic inhibition of NOX2 to elucidate the role of NOX2 for the hematogenous metastasis of melanoma cells...
July 31, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28733349/constitutive-ido1-expression-in-human-tumors-is-driven-by-cyclooxygenase-2-and-mediates-intrinsic-immune-resistance
#17
Marc Hennequart, Luc Pilotte, Stefania Cane, Delia Hoffmann, Vincent Stroobant, Etienne De Plaen, Benoît J Van den Eynde
Tumors use various mechanisms to avoid immune destruction. Cyclooxygenase-2 (COX-2) expression may be a driver of immune suppression in melanoma, but the mechanisms involved remain elusive. Here, we show that COX-2 expression drives constitutive expression of indoleamine 2,3-dioxygenase 1 (IDO1) in human tumor cells. IDO1 is an immunosuppressive enzyme that degrades tryptophan. In a series of seven human tumor lines, constitutive IDO1 expression depends on COX-2 and prostaglandin E2 (PGE2), which, upon autocrine signaling through the EP receptor, activates IDO1 via the PKC and PI3K pathways...
July 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28970357/what-we-re-reading-article-recommendations-from-our-deputy-and-senior-editors
#18
(no author information available yet)
No abstract text is available yet for this article.
October 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28912369/customized-viral-immunotherapy-for-hpv-associated-cancer
#19
Matthew J Atherton, Kyle B Stephenson, Jonathan Pol, Fuan Wang, Charles Lefebvre, David F Stojdl, Jake K Nikota, Anna Dvorkin-Gheva, Andrew Nguyen, Lan Chen, Stephanie Johnson-Obaseki, Patrick J Villeneuve, Jean-Simon Diallo, Jim Dimitroulakos, Yonghong Wan, Brian D Lichty
The viral-transforming proteins E6 and E7 make human papillomavirus-positive (HPV(+)) malignancies an attractive target for cancer immunotherapy. However, therapeutic vaccination exerts limited efficacy in the setting of advanced disease. We designed a strategy to induce substantial specific immune responses against multiple epitopes of E6 and E7 proteins based on an attenuated transgene from HPV serotypes 16 and 18 that is incorporated into MG1-Maraba virotherapy (MG1-E6E7). Mutations introduced to the transgene abrogate the ability of E6 and E7 to perturb p53 and retinoblastoma, respectively, while maintaining the ability to invoke tumor-specific, multifunctional CD8(+) T-cell responses...
October 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28903971/extracellular-s100a9-protein-in-bone-marrow-supports-multiple-myeloma-survival-by-stimulating-angiogenesis-and-cytokine-secretion
#20
Kim De Veirman, Nathan De Beule, Ken Maes, Eline Menu, Elke De Bruyne, Hendrik De Raeve, Karel Fostier, Jérôme Moreaux, Alboukadel Kassambara, Dirk Hose, Roy Heusschen, Helena Eriksson, Karin Vanderkerken, Els Van Valckenborgh
Dysregulated expression of S100 protein family members is associated with cancer proliferation, invasion, angiogenesis, and inflammation. S100A9 induces myeloid-derived suppressor cell (MDSC) accumulation and activity. MDSCs, immunosuppressive cells that contribute to tumor immune escape, are the main producers of S100A9. In this study, we evaluated the role of extracellular S100A9 and the therapeutic relevance of S100A9 inhibition in multiple myeloma (MM), using the immunocompetent murine 5T33MM model. We demonstrated the presence of S100A9 and its receptor TLR4 in both monocytic and granulocytic MDSCs in human and mouse samples...
October 2017: Cancer Immunology Research
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