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Cancer Immunology, Immunotherapy: CII

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https://www.readbyqxmd.com/read/28918459/hla-class-i-expression-predicts-prognosis-and-therapeutic-benefits-from-tyrosine-kinase-inhibitors-in-metastatic-renal-cell-carcinoma-patients
#1
Jiajun Wang, Li Liu, Yang Qu, Wei Xi, Yu Xia, Qi Bai, Ying Xiong, Qilai Long, Jiejie Xu, Jianming Guo
PURPOSE: Classical HLA class I antigen is highly involved in antigen presentation and adaptive immune response against tumor. In this study, we explored its predictive value for treatment response and survival in metastatic renal-cell carcinoma (mRCC) patients. EXPERIMENTAL DESIGN: A TKI cohort of 111 mRCC patients treated with sunitinib or sorafenib and a non-TKI cohort of 160 mRCC patients treated with interleukin-2 or interferon-α-based immunotherapy at a single institution were retrospectively enrolled...
September 16, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28916862/monitoring-the-response-of-urothelial-precancerous-lesions-to-bacillus-calmette-guerin-at-the-proteome-level-in-an-in-vivo-rat-model
#2
Kerem Teke, Nil Guzel, Ali Kemal Uslubas, Murat Kasap, Hasan Yilmaz, Gurler Akpinar, Demir Kursat Yildiz, Ozdal Dillioglugil
Intravesical Bacillus Calmette-Guerin (BCG) is the best treatment modality for progression of non-muscle invasive bladder cancer. We aimed to monitor changes at the proteome level to identify putative protein biomarkers associated with the response of urothelial precancerous lesions to intravesical BCG treatment. The rats were divided into three groups (n = 10/group): control, non-treated, and BCG-treated groups. The non-treated and BCG-treated groups received N-methyl-N-nitrosourea intravesically. BCG Tice-strain was instilled into bladder in BCG-treated group...
September 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28913619/bile-duct-obstruction-in-a-patient-treated-with-nivolumab-as-second-line-chemotherapy-for-advanced-non-small-cell-lung-cancer-a-case-report
#3
Jumpei Kashima, Yusuke Okuma, Ryoko Shimizuguchi, Kazuro Chiba
Immune checkpoint inhibitors (ICIs) are becoming a standard therapy for non-small-cell lung cancer in the advanced stage. As these ICIs become widely available in clinical practice, immune-related adverse effects will become more common. Here we report a patient with lung adenocarcinoma who was treated with nivolumab and developed obstruction because of biliary inflammation. A 63-year-old Japanese man having lung adenocarcinoma with pleural dissemination complained of epigastric pain on the fifth cycle of nivolumab...
September 14, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28905118/administration-of-low-dose-combination-anti-ctla4-anti-cd137-and-anti-ox40-into-murine-tumor-or-proximal-to-the-tumor-draining-lymph-node-induces-systemic-tumor-regression
#4
Jonathan P O Hebb, Adriane R Mosley, Felipe Vences-Catalán, Narendiran Rajasekaran, Anna Rosén, Peter Ellmark, Dean W Felsher
The delivery of immunomodulators directly into the tumor potentially harnesses the existing antigen, tumor-specific infiltrating lymphocytes, and antigen presenting cells. This can confer specificity and generate a potent systemic anti-tumor immune response with lower doses and less toxicity compared to systemic administration, in effect an in situ vaccine. Here, we test this concept using the novel combination of immunomodulators anti-CTLA4, -CD137, and -OX40. The triple combination administered intratumorally at low doses to one tumor of a dual tumor mouse model had dramatic local and systemic anti-tumor efficacy in lymphoma (A20) and solid tumor (MC38) models, consistent with an abscopal effect...
September 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28894934/tumor-infiltrating-lymphocytes-in-lymph-node-metastases-of-stage-iii-melanoma-correspond-to-response-and-survival-in-nine-patients-treated-with-ipilimumab-at-the-time-of-stage-iv-disease
#5
Stefan Diem, Omar Hasan Ali, Christoph J Ackermann, David Bomze, Viktor H Koelzer, Wolfram Jochum, Daniel E Speiser, Kirsten D Mertz, Lukas Flatz
Prognosis of metastatic melanoma improved with the development of checkpoint inhibitors. The role of tumor infiltrating lymphocytes (TILs) in lymph node metastases of stage III melanoma remains unclear. We retrospectively characterized TILs in primary melanomas and matched lymph node metastases (stage III melanoma) of patients treated with the checkpoint inhibitor ipilimumab. Tumor infiltrating lymphocytes were characterized for CD3, CD4, and CD8 expressions by immunohistochemistry. 4/9 patients (44%) responded to treatment with ipilimumab (1 complete and 2 partial remissions, 1 stable disease)...
September 11, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28884365/transcriptomic-analysis-of-the-tumor-microenvironment-to-guide-prognosis-and-immunotherapies
#6
REVIEW
Florent Petitprez, Yann A Vano, Etienne Becht, Nicolas A Giraldo, Aurélien de Reyniès, Catherine Sautès-Fridman, Wolf H Fridman
Tumors are highly heterogeneous tissues where malignant cells are surrounded by and interact with a complex tumor microenvironment (TME), notably composed of a wide variety of immune cells, as well as vessels and fibroblasts. As the dialectical influence between tumor cells and their TME is known to be clinically crucial, we need tools that allow us to study the cellular composition of the microenvironment. In this focused research review, we report MCP-counter, a methodology based on transcriptomic markers that assesses the proportion of several immune and stromal cell populations in the TME from transcriptomic data, and we highlight how it can provide a way to decipher the complex mechanisms at play in tumors...
September 7, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28879551/clinical-grade-manufacturing-of-genetically-modified-car-expressing-nk-92-cells-for-the-treatment-of-erbb2-positive-malignancies
#7
Paulina Nowakowska, Annette Romanski, Nicole Miller, Marcus Odendahl, Halvard Bonig, Congcong Zhang, Erhard Seifried, Winfried S Wels, Torsten Tonn
BACKGROUND: The NK-92/5.28.z cell line (also referred to as HER2.taNK) represents a stable, lentiviral-transduced clone of ErbB2 (HER2)-specific, second-generation CAR-expressing derivative of clinically applicable NK-92 cells. This study addresses manufacturing-related issues and aimed to develop a GMP-compliant protocol for the generation of NK-92/5.28.z therapeutic doses starting from a well-characterized GMP-compliant master cell bank. MATERIALS AND METHODS: Commercially available GMP-grade culture media and supplements (fresh frozen plasma, platelet lysate) were evaluated for their ability to support expansion of NK-92/5...
September 6, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28875329/the-stat3-inhibitor-pyrimethamine-displays-anti-cancer-and-immune-stimulatory-effects-in-murine-models-of-breast-cancer
#8
Mohammad W Khan, Abdulrahman Saadalla, Ahmed H Ewida, Khalid Al-Katranji, Ghadier Al-Saoudi, Zachary T Giaccone, Fotini Gounari, Ming Zhang, David A Frank, Khashayarsha Khazaie
The transcription factor signal activator and transducer or transcription (STAT3), which regulates genes controlling proliferation, survival, and invasion, is activated inappropriately in many human cancers, including breast cancer. Activation of STAT3 can lead to both malignant cellular behavior and suppression of immune cell function in the tumor microenvironment. Through a chemical-biology screen, pyrimethamine (PYR), an FDA approved anti-microbial drug, was identified as an inhibitor of STAT3 function at concentrations known to be achieved safely in humans...
September 5, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28871365/immune-profiling-of-melanoma-tumors-reflecting-aggressiveness-in-a-preclinical-model
#9
Sotirios P Fortis, Louisa G Mahaira, Eleftheria A Anastasopoulou, Ioannis F Voutsas, Sonia A Perez, Constantin N Baxevanis
Melanoma, like most solid tumors, is highly heterogeneous in terms of invasive, proliferative, and tumor-initiating potential. This heterogeneity is the outcome of differential gene expression resulting from conditions in the tumor microenvironment and the selective pressure of the immune system. To investigate possible signatures combining immune-related gene expression and lymphocyte infiltration, we established a preclinical model using B16.F1-derived clones, in the context of melanoma aggressiveness. Combinatorial analyses revealed that tumors concomitantly expressing low levels of Tnf-a, Pd-1, Il-10, Il-1ra, Ccl5, Ido, high Il-9, and with low infiltration by CD45(+), CD3(+), CD4(+) and CD8(+) cells and a high CD4(+):CD8(+) T cell ratio exhibited the most aggressive growth characteristics...
September 4, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28856441/toll-like-receptor-5-and-7-expression-may-impact-prognosis-of-hpv-positive-oropharyngeal-squamous-cell-carcinoma-patients
#10
Lauri Jouhi, Hesham Mohamed, Antti Mäkitie, Satu Maria Remes, Caj Haglund, Timo Atula, Jaana Hagström
A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and innate immunity. We examined the expression of TLRs in OPSCC, and their association with HPV status and treatment outcome. TLR 5, 7, 9, and p16 were studied by immunohistochemistry and HPV status was detected with in situ hybridization in 202 tumors of consecutively treated OPSCC patients using tissue microarray method...
August 30, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28856392/ctla-4-cd80-pathway-regulates-t-cell-infiltration-into-pancreatic-cancer
#11
Fee Bengsch, Dawson M Knoblock, Anni Liu, Florencia McAllister, Gregory L Beatty
The ability of some tumors to exclude effector T cells represents a major challenge to immunotherapy. T cell exclusion is particularly evident in pancreatic ductal adenocarcinoma (PDAC), a disease where blockade of the immune checkpoint molecule CTLA-4 has not produced significant clinical activity. In PDAC, effector T cells are often scarce within tumor tissue and confined to peritumoral lymph nodes and lymphoid aggregates. We hypothesized that CTLA-4 blockade, despite a lack of clinical efficacy seen thus far in PDAC, might still alter T cell immunobiology, which would have therapeutic implications...
August 30, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28840297/therapeutic-antibodies-against-cancer-stem-cells-a-promising-approach
#12
REVIEW
Smarakan Sneha, Rohit Pravin Nagare, Syama Krishna Priya, Chirukandath Sidhanth, Klaus Pors, Trivadi Sundaram Ganesan
Monoclonal antibodies have been extensively used to treat malignancy along with routine chemotherapeutic drugs. Chemotherapy for metastatic cancer has not been successful in securing long-term remission of disease. This is in part due to the resistance of cancer cells to drugs. One aspect of the drug resistance is the inability of conventional drugs to eliminate cancer stem cells (CSCs) which often constitute less than 1-2% of the whole tumor. In some tumor types, it is possible to identify these cells using surface markers...
August 24, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28828629/interleukin-6-induces-m2-macrophage-differentiation-by-stat3-activation-that-correlates-with-gastric-cancer-progression
#13
Xiao-Long Fu, Wei Duan, Chong-Yu Su, Fang-Yuan Mao, Yi-Ping Lv, Yong-Sheng Teng, Pei-Wu Yu, Yuan Zhuang, Yong-Liang Zhao
Interleukin 6 (IL-6) was abundant in the tumor microenvironment and played potential roles in tumor progression. In our study, the expression of IL-6 in tumor tissues from 36 gastric cancer (GC) patients was significantly higher than in non-tumor tissues. Moreover, the number of CD163(+)CD206(+) M2 macrophages that infiltrated in tumor tissues was significantly greater than those infiltrated in non-tumor tissues. The frequencies of M2 macrophages were positively correlated with the IL-6 expression in GC tumors...
August 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28825123/regulatory-t-cell-subsets-in-patients-with-medulloblastoma-at-diagnosis-and-during-standard-irradiation-and-chemotherapy-pbtc-n-11
#14
Sridharan Gururangan, Elizabeth Reap, Robert Schmittling, Mehmet Kocak, Renee Reynolds, Gerald Grant, Arzu Onar-Thomas, Patricia Baxter, Ian F Pollack, Peter Phillips, James Boyett, Maryam Fouladi, Duane Mitchell
BACKGROUND: We evaluated circulating levels of immunosuppressive regulatory T cells (Tregs) and other lymphocyte subsets in patients with newly diagnosed medulloblastoma (MBL) undergoing surgery compared to a control cohort of patients undergo craniectomy for correction of Chiari malformation (CM) and further determined the impact of standard irradiation and chemotherapy on this cell population. METHODS: Eligibility criteria for this biologic study included age 4-21 years, patients with CM undergoing craniectomy (as non-malignant surgical controls) and receiving dexamethasone for prevention of post-operative nausea, and those with newly diagnosed posterior fossa tumors (PFT) undergoing surgical resection and receiving dexamethasone as an anti-edema measure...
August 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28819703/novel-prostate-cancer-immunotherapy-with-a-dna-encoded-anti-prostate-specific-membrane-antigen-monoclonal-antibody
#15
Kar Muthumani, Liron Marnin, Sagar B Kudchodkar, Alfredo Perales-Puchalt, Hyeree Choi, Sangya Agarwal, Veronica L Scott, Emma L Reuschel, Faraz I Zaidi, Elizabeth K Duperret, Megan C Wise, Kimberly A Kraynyak, Kenneth E Ugen, Niranjan Y Sardesai, J Joseph Kim, David B Weiner
Prostate-specific membrane antigen (PSMA) is expressed at high levels on malignant prostate cells and is likely an important therapeutic target for the treatment of prostate carcinoma. Current immunotherapy approaches to target PSMA include peptide, cell, vector or DNA-based vaccines as well as passive administration of PSMA-specific monoclonal antibodies (mAb). Conventional mAb immunotherapy has numerous logistical and practical limitations, including high production costs and a requirement for frequent dosing due to short mAb serum half-life...
August 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28798979/mucosa-associated-invariant-t-cells-infiltrate-hepatic-metastases-in-patients-with-colorectal-carcinoma-but-are-rendered-dysfunctional-within-and-adjacent-to-tumor-microenvironment
#16
Christopher R Shaler, Mauro E Tun-Abraham, Anton I Skaro, Khashayarsha Khazaie, Alexandra J Corbett, Tina Mele, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Mucosa-associated invariant T (MAIT) cells are innate-like T lymphocytes that are unusually abundant in the human liver, a common site of colorectal carcinoma (CRC) metastasis. However, whether they contribute to immune surveillance against colorectal liver metastasis (CRLM) is essentially unexplored. In addition, whether MAIT cell functions can be impacted by chemotherapy is unclear. These are important questions given MAIT cells' potent immunomodulatory and inflammatory properties. Herein, we examined the frequencies and functions of peripheral blood, healthy liver tissue, tumor-margin and tumor-infiltrating MAIT cells in 21 CRLM patients who received no chemotherapy, FOLFOX, or a combination of FOLFOX and Avastin before they underwent liver resection...
August 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28795218/atopy-and-prostate-cancer-is-there-a-link-between-circulating-levels-of-ige-and-psa-in-humans
#17
Mieke Van Hemelrijck, Sophia N Karagiannis, Sabine Rohrmann
BACKGROUND: Atopy has been investigated as a potential risk factor for prostate cancer. IgE antibodies may be major players in protective responses against tumours, through engendering antigen presentation and enhancing adaptive immune responses targeted towards a specific allergen, but potentially also against tumour-associated antigens such as prostate-specific antigen (PSA). We therefore cross-sectionally investigated associations between circulating levels of PSA and IgE in the National Health and Nutrition Examination Survey 2005-2006...
August 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28776079/evaluation-of-a-xenogeneic-vascular-endothelial-growth-factor-2-vaccine-in-two-preclinical-metastatic-tumor-models-in-mice
#18
Sofie Denies, Bregje Leyman, Hanne Huysmans, Francis Combes, Séan Mc Cafferty, Laetitia Cicchelero, Marjan Steppe, Joyca De Temmerman, Niek N Sanders
In this study, a xenogeneic DNA vaccine encoding for human vascular endothelial growth factor receptor-2 (hVEGFR-2) was evaluated in two murine tumor models, the B16-F10 melanoma and the EO771 breast carcinoma model. The vaccine was administered by intradermal injection followed by electroporation. The immunogenicity and the biological efficacy of the vaccine were tested in (1) a prophylactic setting, (2) a therapeutic setting, and (3) a therapeutic setting combined with surgical removal of the primary tumor...
August 3, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28770278/an-unbiased-in-vivo-functional-genomics-screening-approach-in-mice-identifies-novel-tumor-cell-based-regulators-of-immune-rejection
#19
Casey W Shuptrine, Reham Ajina, Elana J Fertig, Sandra A Jablonski, H Kim Lyerly, Zachary C Hartman, Louis M Weiner
The clinical successes of immune checkpoint therapies for cancer make it important to identify mechanisms of resistance to anti-tumor immune responses. Numerous resistance mechanisms have been identified employing studies of single genes or pathways, thereby parsing the tumor microenvironment complexity into tractable pieces. However, this limits the potential for novel gene discovery to in vivo immune attack. To address this challenge, we developed an unbiased in vivo genome-wide RNAi screening platform that leverages host immune selection in strains of immune-competent and immunodeficient mice to select for tumor cell-based genes that regulate in vivo sensitivity to immune attack...
August 2, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28755091/car-t-cells-targeting-solid-tumors-carcinoembryonic-antigen-cea-proves-to-be-a-safe-target
#20
LETTER
Astrid Holzinger, Hinrich Abken
No abstract text is available yet for this article.
July 28, 2017: Cancer Immunology, Immunotherapy: CII
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