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Cancer Immunology Research

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https://www.readbyqxmd.com/read/28108630/macropinocytosis-of-nab-paclitaxel-drives-macrophage-activation-in-pancreatic-cancer
#1
Jane E Cullis, Despina Siolas, Antonina Avanzi, Sugata Barui, Anirban Maitra, Dafna Bar-Sagi
Pancreatic cancer is a devastating disease that is largely refractory to currently available treatment strategies. Therapeutic resistance is partially attributed to the dense stromal reaction of PDAC tumors that includes a pervasive infiltration of immunosuppressive (M2) macrophages. Nab-paclitaxel (trade name Abraxane) is a nanoparticle albumin-bound formulation of paclitaxel that, in combination with gemcitabine, is currently the first line treatment for pancreatic cancer. Here, we show that macrophages internalized nab-paclitaxel via macropinocytosis...
January 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28108629/myeloid-stat3-promotes-lung-tumorigenesis-by-transforming-tumor-immunosurveillance-into-tumor-promoting-inflammation
#2
Jingjiao Zhou, Zhaoxia Qu, Fan Sun, Lei Han, Liwen Li, Shapei Yan, Laura P Stabile, Lin-Feng Chen, Jill M Siegfried, Gutian Xiao
One of the most fundamental and challenging questions in the cancer field is how immunity in cancer patients is transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identify the transcription factor STAT3 as the culprit responsible for this pathogenic event in lung cancer development. We found that antitumor type 1 CD4(+) T helper (Th1) cells and CD8(+) T cells were directly counter-balanced in lung cancer development with tumor-promoting myeloid-derived suppressor cells (MDSCs) and suppressive macrophages, and that activation of STAT3 in MDSCs and macrophages promoted tumorigenesis through pulmonary recruitment and increased resistance of suppressive cells to CD8(+) T cells, enhancement of cytotoxicity towards CD4(+) and CD8(+) T cells, induction of regulatory T cell (Treg), inhibition of dendritic cells (DCs), and polarization of macrophages toward the M2 phenotype...
January 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28093447/inflammasomes-and-cancer
#3
Rajendra Karki, Si Ming Man, Thirumala-Devi Kanneganti
Inflammation affects all stages of tumorigenesis. A key signaling pathway leading to acute and chronic inflammation is through activation of the caspase-1 inflammasome. Inflammasome complexes are assembled on activation of certain nucleotide-binding domain, leucine-rich repeat-containing proteins (NLR), AIM2-like receptors, or pyrin. Of these, NLRP1, NLRP3, NLRC4, NLRP6, and AIM2 influence the pathogenesis of cancer by modulating innate and adaptive immune responses, cell death, proliferation, and/or the gut microbiota...
January 16, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28093446/tumor-infiltrating-merkel-cell-polyomavirus-specific-t-cells-are-diverse-and-associated-with-improved-patient-survival
#4
Natalie J Miller, Candice D Church, Lichun Dong, David Crispin, Matthew P Fitzgibbon, Kristina Lachance, Lichen Jing, Michi Shinohara, Ioannis Gavvovidis, Gerald Willimsky, Martin McIntosh, Thomas Blankenstein, David M Koelle, Paul Nghiem
Tumor-infiltrating CD8(+) T cells are associated with improved survival of patients with Merkel cell carcinoma (MCC), an aggressive skin cancer causally linked to Merkel cell polyomavirus (MCPyV). However, CD8(+) T-cell infiltration is robust in only 4% to 18% of MCC tumors. We characterized the T-cell receptor (TCR) repertoire restricted to one prominent epitope of MCPyV (KLLEIAPNC, "KLL") and assessed whether TCR diversity, tumor infiltration, or T-cell avidity correlated with clinical outcome. HLA-A*02:01/KLL tetramer(+) CD8(+) T cells from MCC patient peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TIL) were isolated via flow cytometry...
January 16, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28077434/transfer-of-allogeneic-cd4-t-cells-rescues-cd8-t-cells-in-anti-pd-l1-resistant-tumors-leading-to-tumor-eradication
#5
Ainhoa Arina, Theodore G Karrison, Eva Galka, Karin Schreiber, Ralph R Weichselbaum, Hans Schreiber
Adoptively transferred CD8(+) T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T cell-mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule K(b) needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8(+) T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months...
January 11, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28073775/dasatinib-changes-immune-cell-profiles-concomitant-with-reduced-tumor-growth-in-several-murine-solid-tumor-models
#6
Can Hekim, Mette Ilander, Jun Yan, Erin Michaud, Richard Smykla, Markus Vähä-Koskela, Paula Savola, Siri Tähtinen, Leena Saikko, Akseli Hemminki, Panu E Kovanen, Kimmo Porkka, Francis Yf Lee, Satu Mustjoki
Dasatinib, a broad range tyrosine kinase inhibitor (TKI), induces rapid mobilization of lymphocytes and clonal expansion of cytotoxic cells in leukemia patients. Here, we investigated whether dasatinib could induce beneficial immunomodulatory effects in solid tumor models. The effects on tumor growth and on the immune system were studied in four different syngeneic mouse models (B16.OVA melanoma, 1956 sarcoma, MC38 colon, and 4T1 breast carcinoma). Both peripheral blood (PB) and tumor samples were immunophenotyped during treatment...
January 10, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28073774/temporally-distinct-pd-l1-expression-by-tumor-and-host-cells-contributes-to-immune-escape
#7
Takuro Noguchi, Jeffrey P Ward, Matthew M Gubin, Cora D Arthur, Sang Hun Lee, Jasreet Hundal, Mark J Selby, Robert F Graziano, Elaine R Mardis, Alan J Korman, Robert D Schreiber
Antibody blockade of programmed death-1 (PD-1) or its ligand, PD-L1, has led to unprecedented therapeutic responses in certain tumor-bearing individuals, but PD-L1 expression's prognostic value in stratifying cancer patients for such treatment remains unclear. Reports conflict on the significance of correlations between PD-L1 on tumor cells and positive clinical outcomes to PD-1/PD-L1 blockade. We investigated this issue using genomically related, clonal subsets from the same methylcholanthrene-induced sarcoma: a highly immunogenic subset that is spontaneously eliminated in vivo by adaptive immunity and a less immunogenic subset that forms tumors in immunocompetent mice, but is sensitive to PD-1/PD-L1 blockade therapy...
January 10, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28073773/long-term-survival-and-clinical-benefit-from-adoptive-t-cell-transfer-in-stage-iv-melanoma-patients-is-determined-by-a-four-parameter-tumor-immune-signature
#8
Sara M Melief, Valeria V Visconti, Marten Visser, Merel van Diepen, Ellen H W Kapiteijn, Joost H van den Berg, John B A G Haanen, Vincent T H B M Smit, Jan Oosting, Sjoerd H van der Burg, Els M E Verdegaal
The presence of tumor-infiltrating immune cells is associated with longer survival and a better response to immunotherapy in early-stage melanoma, but a comprehensive study of the in situ immune microenvironment in stage IV melanoma has not been performed. We investigated the combined influence of a series of immune factors on survival and response to adoptive cell transfer (ACT) in stage IV melanoma patients. Metastases of 73 stage IV melanoma patients, 17 of which were treated with ACT, were studied with respect to the number and functional phenotype of lymphocytes and myeloid cells as well as for expression of galectins-1, -3, and -9...
January 10, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28062513/metastatic-melanoma-patient-had-complete-response-with-clonal-expansion-after-whole-brain-radiation-and-pd-1-blockade
#9
Cara L Haymaker, DaeWon Kim, Marc Uemura, Luis M Vence, Ann Phillip, Natalie McQuail, Paul D Brown, Irina Fernandez, Courtney W Hudgens, Caitlin Creasy, Wen-Jen Hwu, Padmanee Sharma, Michael T Tetzlaff, James P Allison, Patrick Hwu, Chantale Bernatchez, Adi Diab
We report here on a patient with metastatic melanoma who had extensive brain metastases. After being treated with the sequential combination of whole brain radiation therapy (WBRT) followed by the PD-1 inhibitory antibody, pembrolizumab, the patient had a durable complete response. Retrospective laboratory studies of T cells revealed that, after treatment with anti-PD-1 commenced, effector CD8(+) T cells in the blood expanded and the ratio of CD8(+):Treg T cells increased. A CD8(+) T-cell clone present in the initial brain metastases was expanded in the blood after anti-PD-1 treatment, which suggested an antitumor role for this clone...
January 6, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28039162/infiltration-of-cd8-t-cells-and-expression-of-pd-1-and-pd-l1-in-synovial-sarcoma
#10
Theodore S Nowicki, Ryan Akiyama, Rong Rong Huang, I Peter Shintaku, Xiaoyan Wang, Paul C Tumeh, Arun Singh, Bartosz Chmielowski, Christopher Denny, Noah Federman, Antoni Ribas
Tumors expressing programmed death ligand 1 (PD-L1) interact with the corresponding negative-signal generating immune receptor on the surface of CD8 T cells, PD-1, thereby suppressing antitumor activity. Therapeutics blocking this interaction have shown promise in various cancers by restoring functional antitumor T-cell activity. We explored the degree of PD-L1, PD-1, and CD8 expression in a retrospective analysis of 29 clinical synovial sarcoma samples. Quantitative immunohistochemistry and multiplex immunofluorescence were used to determine relative quantification of CD8(+) and PD-1(+) T cells and PD-L1 expression within the intratumor area and the interface between the tumor and the surrounding nontumor tissue (i...
December 30, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/28039161/the-different-t-cell-receptor-repertoires-in-breast-cancer-tumors-draining-lymph-nodes-and-adjacent-tissues
#11
Ting Wang, Changxi Wang, Jinghua Wu, Chenyang He, Wei Zhang, Jiayun Liu, Ruifang Zhang, Yonggang Lv, Yongping Li, Xiaojing Zeng, Hongzhi Cao, Xiuqing Zhang, Xun Xu, Chen Huang, Ling Wang, Xiao Liu
T lymphocytes infiltrate the microenvironment of breast cancer (BC) tumors and play a pivotal role in tumor immune surveillance. Relationships between the T-cell receptors (TCRs) borne by T cells within tumors, in the surrounding tissues, and in draining lymph nodes are largely unexplored in human breast cancer. Consequently, information about the relative extent of possible T-cell exchange between these tissues is also lacking. Here we have analyzed the TCR repertoire of T cells using multiplex PCR and high throughput sequencing of the TCRβ chain in the tissues of tumor, adjacent nontumor, and axillary lymph-nodes of breast cancer patients...
December 30, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27923825/rational-selection-of-syngeneic-preclinical-tumor-models-for-immunotherapeutic-drug-discovery
#12
Suzanne I S Mosely, John E Prime, Richard C A Sainson, Jens-Oliver Koopmann, Dennis Y Q Wang, Danielle M Greenawalt, Miika J Ahdesmaki, Rebecca Leyland, Stefanie Mullins, Luciano Pacelli, Danielle Marcus, Judith Anderton, Amanda Watkins, Jane Coates Ulrichsen, Philip Brohawn, Brandon W Higgs, Matthew McCourt, Hazel Jones, James A Harper, Michelle Morrow, Viia Valge-Archer, Ross Stewart, Simon J Dovedi, Robert W Wilkinson
Murine syngeneic tumor models are critical to novel immuno-based therapy development, but the molecular and immunologic features of these models are still not clearly defined. The translational relevance of differences between the models is not fully understood, impeding appropriate preclinical model selection for target validation, and ultimately hindering drug development. Across a panel of commonly used murine syngeneic tumor models, we showed variable responsiveness to immunotherapies. We used array comparative genomic hybridization, whole-exome sequencing, exon microarray analysis, and flow cytometry to extensively characterize these models, which revealed striking differences that may underlie these contrasting response profiles...
December 6, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27923824/human-dendritic-cells-mitigate-nk-cell-dysfunction-mediated-by-nonselective-jak1-2-blockade
#13
Shane A Curran, Justin A Shyer, Erin T St Angelo, Lillian R Talbot, Sneh Sharma, David J Chung, Glenn Heller, Katharine C Hsu, Brian C Betts, James W Young
Janus kinase (JAK) inhibitors have achieved positive responses in myeloproliferative neoplasms, but at the expense of decreased natural killer (NK) cell numbers and compromised function. Selective JAK2 inhibition may also have a role in preventing and treating graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Although JAK inhibitors can impair monocyte-derived dendritic cell (moDC) activation and function and suppress effector T-cell responses, the effects on NK cells and the relevant mechanisms remain undefined...
December 6, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27923823/bortezomib-relieves-immune-tolerance-in-nasopharyngeal-carcinoma-via-stat1-suppression-and-indoleamine-2-3-dioxygenase-downregulation
#14
Guan-Min Jiang, Hong-Sheng Wang, Jun Du, Wei-Feng Ma, Hui Wang, Yu Qiu, Qiu-Gui Zhang, Wei Xu, Hui-Fang Liu, Jian-Ping Liang
Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC). Patients with intermediate and advanced stage NPC receiving only radiotherapy have limited survival, so newer immunotherapeutic approaches are sought. The major impediment to better clinical outcomes is tumor immune tolerance. Indoleamine 2,3-dioxygenase (IDO), an IFNγ-inducible enzyme, is a major inducer of immune tolerance during tumor development; therefore, inhibition of the IDO pathway is an important modality for cancer treatment...
December 6, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27920023/il4-from-t-follicular-helper-cells-downregulates-antitumor-immunity
#15
Hidekazu Shirota, Dennis M Klinman, Shuku-Ei Ito, Hiroyasu Ito, Masato Kubo, Chikashi Ishioka
Immune cells constitute a large fraction of the tumor microenvironment and modulate tumor progression. Clinical data indicate that chronic inflammation is present at tumor sites and that IL4 in particular is upregulated. Here, we demonstrate that T follicular helper (Tfh) cells arise in tumor-draining lymph nodes where they produce an abundance of IL4. Deletion of IL4-expressing Tfh cells improves antitumor immunity, delays tumor growth, and reduces the generation of immunosuppressive myeloid cells in the lymph nodes...
December 5, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/28052991/myeloid-derived-suppressor-cells
#16
REVIEW
Dmitry I Gabrilovich
Myeloid cells developed evolutionarily as a major mechanism to protect the host. They evolved as a critical barrier against infections and are important contributors to tissue remodeling. However, in cancer, myeloid cells are largely converted to serve a new master-tumor cells. This process is epitomized by myeloid-derived suppressor cells (MDSC). These cells are closely related to neutrophils and monocytes. MDSCs are not present in the steady state of healthy individuals and appear in cancer and in pathologic conditions associated with chronic inflammation or stress...
January 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28052990/about-the-master
#17
REVIEW
(no author information available yet)
No abstract text is available yet for this article.
January 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28052989/article-recommendations-from-our-deputy-and-senior-editors
#18
(no author information available yet)
No abstract text is available yet for this article.
January 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28003187/angiopoietin-2-as-a-biomarker-and-target-for-immune-checkpoint-therapy
#19
Xinqi Wu, Anita Giobbie-Hurder, Xiaoyun Liao, Courtney Connelly, Erin M Connolly, Jingjing Li, Michael P Manos, Donald Lawrence, David McDermott, Mariano Severgnini, Jun Zhou, Evisa Gjini, Ana Lako, Mikel Lipschitz, Christine J Pak, Sara Abdelrahman, Scott Rodig, F Stephen Hodi
Immune checkpoint therapies targeting CTLA-4 and PD-1 have proven effective in cancer treatment. However, the identification of biomarkers for predicting clinical outcomes and mechanisms to overcome resistance remain as critical needs. Angiogenesis is increasingly appreciated as an immune modulator with potential for combinatorial use with checkpoint blockade. Angiopoietin-2 (ANGPT2) is an immune target in patients and is involved in resistance to anti-VEGF treatment with the monoclonal antibody bevacizumab...
January 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/27956380/somatic-mutations-and-neoepitope-homology-in-melanomas-treated-with-ctla-4-blockade
#20
Tavi Nathanson, Arun Ahuja, Alexander Rubinsteyn, Bulent Arman Aksoy, Matthew D Hellmann, Diana Miao, Eliezer Van Allen, Taha Merghoub, Jedd D Wolchok, Alexandra Snyder, Jeff Hammerbacher
Immune checkpoint inhibitors are promising treatments for patients with a variety of malignancies. Toward understanding the determinants of response to immune checkpoint inhibitors, it was previously demonstrated that the presence of somatic mutations is associated with benefit from checkpoint inhibition. A hypothesis was posited that neoantigen homology to pathogens may in part explain the link between somatic mutations and response. To further examine this hypothesis, we reanalyzed cancer exome data obtained from our previously published study of 64 melanoma patients treated with CTLA-4 blockade and a new dataset of RNA-Seq data from 24 of these patients...
January 2017: Cancer Immunology Research
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