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cancer cell,tumor,immune surveilance

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https://www.readbyqxmd.com/read/28537924/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#1
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536458/epigenetic-priming-restores-the-hla-class-i-antigen-processing-machinery-expression-in-merkel-cell-carcinoma
#2
Cathrin Ritter, Kaiji Fan, Annette Paschen, Sine Reker Hardrup, Soldano Ferrone, Paul Nghiem, Selma Ugurel, David Schrama, Jürgen C Becker
Merkel cell carcinoma (MCC) is a rare and aggressive, yet highly immunogenic skin cancer. The latter is due to its viral or UV-associated carcinogenesis. For tumor progression MCC has to escape the host's immuno-surveillance, e.g. by loss of HLA class-I expression. Indeed, a reduced HLA class-I expression was observed in MCC tumor tissues and MCC cell lines. This reduced HLA class-I surface expression is caused by an impaired expression of key components of the antigen processing machinery (APM), including LMP2 and LMP7 as well as TAP1 and TAP2...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28533942/hla-a24-ligandome-analysis-of-colon-and-lung-cancer-cells-identifies-a-novel-cancer-testis-antigen-and-a-neoantigen-that-elicits-specific-and-strong-ctl-responses
#3
Vitaly Kochin, Takayuki Kanaseki, Serina Tokita, Sho Miyamoto, Yosuke Shionoya, Yasuhiro Kikuchi, Daichi Morooka, Yoshihiko Hirohashi, Tomohide Tsukahara, Kazue Watanabe, Shingo Toji, Yasuo Kokai, Noriyuki Sato, Toshihiko Torigoe
This study focused on HLA-A24 and comprehensively analyzed the ligandome of colon and lung cancer cells without the use of MHC-binding in silico prediction algorithms. Affinity purification using the antibody specific to HLA-A24 followed by LC-MS/MS sequencing was used to detect peptides, which harbored the known characteristics of HLA-A24 peptides in terms of length and anchor motifs. Ligandome analysis demonstrated the natural presentation of two different types of novel tumor-associated antigens. The ligandome contained a peptide derived from SUV39H2, a gene found to be expressed in a variety of cancers but not in normal tissues (except for the testis)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28527911/cancer-stem-cells-at-the-forefront-of-personalized-medicine-and-immunotherapy
#4
REVIEW
Micol E Fiori, Lidia Villanova, Ruggero De Maria
Cancer stem cells (CSCs) represent the main target of the current efforts to eradicate cancer, because of their ability to promote metastatic dissemination and survive cytotoxic therapies. Here, we highlight the potential of patient-derived CSCs as an in vitro and in vivo pre-clinical model and of liquid biopsy as a diagnostic, prognostic and predictive tool. We discuss recently developed therapeutic strategies aiming at specifically targeting the cancer stem cell population, particularly focusing on the latest advances in cancer immunotherapy...
May 18, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28526770/therapeutic-ige-antibodies-harnessing-a-macrophage-mediated-immune-surveillance-mechanism-against-cancer
#5
REVIEW
Sophia N Karagiannis, Debra H Josephs, Heather J Bax, James F Spicer
IgG monoclonal antibodies have made significant contributions to cancer therapy, but suffer from several limitations that restrict their effectiveness in unleashing host immune system components against tumors. The development of monoclonal antibodies of an alternative class, namely IgE, may offer enhanced immune surveillance and superior effector cell potency against cancer cells. In our recent article, we elaborate our proof-of-concept studies of a mouse/human chimeric IgE antibody (MOv18 IgE), which is specific for the cancer-associated antigen folate receptor alpha...
May 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28523199/de-novo-pten-mutation-in-a-young-boy-with-cutaneous-vasculitis
#6
Angela Mauro, Ebun Omoyinmi, Neil James Sebire, Angela Barnicoat, Paul Brogan
Phosphatase and tensin homolog (PTEN) is the protein encoded by the PTEN gene (10q23.3). PTEN mutations are related to a variety of rare diseases referred to collectively as PTEN hamartoma tumor syndromes (PHTS), which include Cowden Syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus Syndrome, and Proteus-like syndrome. These diseases are associated with an increased risk of malignancy and for this reason an accurate and early diagnosis is essential in order to institute cancer surveillance. PTEN is a regulator of growth and homeostasis in immune system cells, although there are limited data describing immune dysregulation caused by PTEN mutations...
2017: Case Reports in Pediatrics
https://www.readbyqxmd.com/read/28515351/local-immune-response-depends-on-p16ink4a-status-of-primary-tumor-in-vulvar-squamous-cell-carcinoma
#7
Jacek J Sznurkowski, Anton Żawrocki, Wojciech Biernat
BACKGROUND: The p16Ink4a is not a surrogate marker for high-risk human papilloma virus (HPV) genotypes but indicates better prognosis in vulvar squamous cell carcinoma patients. Our recent study confirmed substantial mismatch between p16Ink4a and high-risk HPV-status as well as revealed that p16Ink4a-overexpression itself is an independent prognostic factor for vulvar cancer. AIM: To determine significance of the tumor infiltrating immune cells and p16Ink4a-status for better outcome of patients with vulvar cancer...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514770/mm-bmscs-induce-na%C3%A3-ve-cd4-t-lymphocytes-dysfunction-through-fibroblast-activation-protein-%C3%AE
#8
Xiaofei Wu, Yadan Wang, Jian Xu, Ting Luo, Jun Deng, Yu Hu
BACKGROUND: The tumor microenvironment plays a major role in multiple myelomas (MM). MM-BMSCs (bone marrow mesenchymal stromal cells) can support tumor growth and immune surveillance escape. On the other hand, fibroblast activation protein α, expressed by cancer stroma cells including BMSCs, has been shown to potentiate epithelial cancers growth and immune suppression. RESULTS: MM-BMSC inhibited proliferation of T cells (P = 0.0138), promoted senescence of T cells (P < 0...
April 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512255/immune-consequences-of-penfluridol-treatment-associated-with-inhibition-of-glioblastoma-tumor-growth
#9
Alok Ranjan, Stephen Wright, Sanjay K Srivastava
Glioblastoma is the most common and lethal brain tumor associated with only 12% median survival rate of patients. Despite the development of advanced surgical, radiation or use of combinations of anti-cancer drugs, treatment for glioblastoma patients is still a challenge. The major contributing factor in glioblastoma progression and resistive nature is its ability to evade the immune surveillance. Hence, modulating the immune system in glioblastoma tumors could be an important strategy for anticancer therapeutics...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28503405/nanoparticle-design-strategies-for-effective-cancer-immunotherapy
#10
Praveena Velpurisiva, Aniket Gad, Brandon Piel, Rahul Jadia, Prakash Rai
Cancer immunotherapy is a rapidly evolving and paradigm shifting treatment modality that adds a strong tool to the collective cancer treatment arsenal. It can be effective even for late stage diagnoses and has already received clinical approval. Tumors are known to not only avoid immune surveillance but also exploit the immune system to continue local tumor growth and metastasis. Because of this, most immunotherapies, particularly those directed against solid cancers, have thus far only benefited a small minority of patients...
2017: J Biomed (Syd)
https://www.readbyqxmd.com/read/28488547/stimulatory-role-of-interleukin-10-in-cd8-t-cells-through-stats-in-gastric-cancer
#11
Jianjun Xi, Mingzheng Xu, Zongchang Song, Hongqiang Li, Shumin Xu, Chunmei Wang, Haihan Song, Jianwen Bai
CD8(+) T cells are considered to be critical in tumor surveillance and elimination. Increased CD8(+) T cell frequency and function is associated with better prognosis in cancer patients. Interleukin 10 is a cytokine with controversial roles in CD8(+) T cell-mediated anti-tumor immunity. We therefore examined the interleukin 10 expression and consumption in CD8(+) T cells harvested from the peripheral blood and resected tumors of gastric cancer patients of stages II-IV. We found that the gastric cancer patients presented significantly elevated frequencies of interleukin 10-expressing cells in both CD4(+) and CD8(+) T cells compared to healthy controls...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28484076/sarcoma-eradication-by-doxorubicin-and-targeted-tnf-relies-upon-cd8-t-cell-recognition-of-a-retroviral-antigen
#12
Philipp Probst, Janine Kopp, Annette Oxenius, Mario P Colombo, Danilo Ritz, Tim Fugmann, Dario Neri
Antibody-cytokine complexes may offer new tools to treat cancer. Here we show how TNF-linked antibodies, which recognize tumor-selective splice isoforms of fibronectin (F8-TNF), can be exploited to eradicate sarcomas in immunocompetent mice. We treated mice bearing WEHI-164 fibrosarcoma with a combination of F8-TNF and doxorubicin, curing the majority of treated animals (29/37). Notably, cured mice were resistant to re-challenge not only by WEHI-164 cells but also heterologous C51 or CT26 colorectal tumor cells in a CD8+ T cell-dependent process...
May 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/28469081/c3d-regulates-immune-checkpoint-blockade-and-enhances-antitumor-immunity
#13
Jeffrey L Platt, Inês Silva, Samuel J Balin, Adam R Lefferts, Evan Farkash, Ted M Ross, Michael C Carroll, Marilia Cascalho
Despite expression of immunogenic polypeptides, tumors escape immune surveillance by engaging T cell checkpoint regulators and expanding Tregs, among other mechanisms. What orchestrates these controls is unknown. We report that free C3d, a fragment of the third component of complement, inside tumor cells - or associated with irradiated tumor cells and unattached to antigen - recruits, accelerates, and amplifies antitumor T cell responses, allowing immunity to reverse or even to prevent tumor growth. C3d enhances antitumor immunity independently of B cells, NK cells, or antibodies, but it does so by increasing tumor infiltrating CD8+ lymphocytes, by depleting Tregs, and by suppressing expression of programmed cell death protein 1 (PD-1) by T cells...
May 4, 2017: JCI Insight
https://www.readbyqxmd.com/read/28459521/breast-cancer-stem-like-cells-can-promote-metastasis-by-activating-platelets-and-down-regulating-antitumor-activity-of-natural-killer-cells
#14
Shuo Wang, Ying Zhang, Weihong Cong, Jie Liu, Yuren Zhang, Huiting Fan, Yonggang Xu, Hongsheng Lin
OBJECTIVE: To investigate whether cancer stem cells (CSCs) more efficiently activating platelets and evading immune surveillance than non-CSCs thus promoting metastasis. METHODS: We enriched and identified sphere-forming cells (SFCs) and coincubated washed platelets with several platelet activators including collagen, 4T1 and SFCs. Platelet-coating tumor cells, platelet activation and TGF-β1 release were analyzed. Then natural kell cells (NK) were incubated with supernatants of different activated platelet samples what we called sample release (SR)...
August 2016: Journal of Traditional Chinese Medicine, Chung i Tsa Chih Ying Wen Pan
https://www.readbyqxmd.com/read/28415565/rad52-deficiency-decreases-development-of-lung-squamous-cell-carcinomas-by-enhancing-immuno-surveillance
#15
Rachel Lieberman, Jing Pan, Qi Zhang, Ming You
RAD52 is involved in homologous recombination and DNA repair. This study focuses on lung cancer progression and how the DNA repair gene, Rad52, enables tumor cells to have sufficient genome integrity, i.e., the ability to repair lethal DNA damage, to avoid cell death. In this report, we analyze the phenotypic differences between wild type and Rad52-/- in inhibition of tumor phenotypes including cell growth, viability, cytolysis, and immune profiling. We demonstrated that loss of Rad52 not only increases the death of cells undergoing carcinogen-induced transformation in vivo, but that Rad52 loss also augments in vivo antitumor activity through an enhanced capacity for direct killing of LLC tumor cells by stimulated Rad52-/- NK and CD8+ T cells...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414726/neem-leaf-glycoprotein-prevents-post-surgical-sarcoma-recurrence-in-swiss-mice-by-differentially-regulating-cytotoxic-t-and-myeloid-derived-suppressor-cells
#16
Madhurima Sarkar, Sarbari Ghosh, Avishek Bhuniya, Tithi Ghosh, Ipsita Guha, Subhasis Barik, Jaydip Biswas, Anamika Bose, Rathindranath Baral
Post-surgical tumor recurrence is a common problem in cancer treatment. In the present study, the role of neem leaf glycoprotein (NLGP), a novel immunomodulator, in prevention of post-surgical recurrence of solid sarcoma was examined. Data suggest that NLGP prevents tumor recurrence after surgical removal of sarcoma in Swiss mice and increases their tumor-free survival time. In NLGP-treated tumor-free mice, increased cytotoxic CD8+ T cells and a decreased population of suppressor cells, especially myeloid-derived suppressor cells (MDSCs) was observed...
2017: PloS One
https://www.readbyqxmd.com/read/28408907/type-i-interferons-and-natural-killer-cell-regulation-in-cancer
#17
REVIEW
Lena Müller, Petra Aigner, Dagmar Stoiber
Type I interferons (IFNs) are known to mediate antitumor effects against several tumor types and have therefore been commonly used in clinical anticancer treatment. However, how IFN signaling exerts its beneficial effects is only partially understood. The clinically relevant activity of type I IFNs has been mainly attributed to their role in tumor immune surveillance. Different mechanisms have been postulated to explain how type I IFNs stimulate the immune system. On the one hand, they modulate innate immune cell subsets such as natural killer (NK) cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28401935/unique-invariant-natural-killer-t-cells-promote-intestinal-polyps-by-suppressing-th1-immunity-and-promoting-regulatory-t-cells
#18
Y Wang, S Sedimbi, L Löfbom, A K Singh, S A Porcelli, S L Cardell
CD1d-restricted invariant natural killer T (iNKT) cells are known as potent early regulatory cells of immune responses. Besides the established roles in the regulation of inflammation and autoimmune disease, studies have shown that iNKT cells have important roles in tumor surveillance and the control of tumor metastasis. Here we found that the absence of iNKT cells markedly decreased the total number of intestinal polyps in APC(Min/+) mice, a model for colorectal cancer. Polyp iNKT cells were enriched for interleukin-10 (IL-10)- and IL-17-producing cells, showed a distinct phenotype being CD4(+), NK1...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28400131/linking-tumor-glycolysis-and-immune-evasion-in-cancer-emerging-concepts-and-therapeutic-opportunities
#19
REVIEW
Shanmugasundaram Ganapathy-Kanniappan
Metabolic reprogramming and immune evasion are two hallmarks of cancer. Metabolic reprogramming is exemplified by cancer's propensity to utilize glucose at an exponential rate which in turn is linked with "aerobic glycolysis", popularly known as the "Warburg effect". Tumor glycolysis is pivotal for the efficient management of cellular bioenergetics and uninterrupted cancer growth. Mounting evidence suggests that tumor glycolysis also plays a key role in instigating immunosuppressive networks that are critical for cancer cells to escape immune surveillance ("immune evasion")...
April 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28391403/cytokine-induced-senescence-for-cancer-surveillance
#20
REVIEW
Thomas Wieder, Ellen Brenner, Heidi Braumüller, Oliver Bischof, Martin Röcken
The immune response is a first-line systemic defense to curb tumorigenesis and metastasis. Much effort has been invested to design antitumor interventions that would boost the immune system in its fight to defeat or contain cancerous growth. Tumor vaccination protocols, transfer of tumor-associated-antigen-specific T cells, T cell activity-regulating antibodies, and recombinant cytokines are counted among a toolbox filled with immunotherapeutic options. Although the mechanistic underpinnings of tumor immune control remain to be deciphered, these are studied with the goal of cancer cell destruction...
April 8, 2017: Cancer Metastasis Reviews
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